liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 35 of 35
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Ali, Neserin
    et al.
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Mattsson, Karin
    Center for Molecular Protein Science, Biochemistry and Structural Biology, Lund University, Lund, Sweden.
    Rissler, Jenny
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Karlsson, Helen Marg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Svensson, Christian R
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Gudmundsson, Anders
    Department of Design Sciences, Ergonomic and Aerosol Technology, Lund University, Lund, Sweden.
    Lindh, Christian H
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Jönsson, Bo A G
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Cedervall, Tommy
    Center for Molecular Protein Science, Biochemistry and Structural Biology, Lund University, Lund, Sweden.
    Kåredal, Monica
    Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
    Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.2016In: Nanotoxicology, ISSN 1743-5390, E-ISSN 1743-5404, Vol. 10, no 2, p. 226-234Article in journal (Refereed)
    Abstract [en]

    Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.

  • 2.
    Bengtsson, Torbjörn
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Gunnarsson, Patrik
    Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Skoglund, Caroline
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Elison, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 263, no 5, p. 558-571Article in journal (Refereed)
    Abstract [en]

    Objective: Several studies support an association between periodontal disease and atherosclerosis with a crucial role for the pathogen Porphyromonas gingivalis. This study aims to investigate the proteolytic and oxidative activity of P. gingivalis on LDL in a whole blood system by using a proteomic approach and analyze the effects of P. gingivalis-modifed LDL on cell proliferation.

    Methods: The cellular effects of P. gingivalis in human whole blood were assessed using lumi-aggregometry analyzing reactive oxygen species (ROS) production and aggregation. Blood was incubated for 30 min with P. gingivalis, whereafter LDL was isolated and a proteomic approach was applied to examine protein expression. LDL-oxidation was determined by analyzing the formation of protein carbonyls. The effects of P. gingivalis-modifed LDL on fibroblast proliferation were studied using the MTS-assay.

    Results: Incubation of whole blood with P. gingivalis caused an extensive aggregation and ROS-production, indicating platelet and leukocyte activation. LDL prepared from the bacteria-exposed blood showed an increased protein oxidation, elevated levels of apoM and formation of two apoB-100 N-terminal fragments. P. gingivalis-modified LDL markedly increased the growth of fibroblasts. Inhibition of gingipain R suppressed the modification of LDL by P. gingivalis.

    Conclusions: The ability of P. gingivalis to change the protein expression and the proliferative capacity of LDL may represent a crucial event in periodontitis-associated atherosclerosis.

  • 3.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Lewander, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Peptide mass fingerprint data from silver stained proteins can be improved by using 2,5-dihydroxybenzoic acid instead of α-cyano-4-hydroxycinnamic acid as matrix in MALDI-TOF MS2007Article in journal (Refereed)
  • 4.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Mörtstedt, Harriet
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Lewander, Andreas
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Note: 2,5-Dihydroxybenzoic acid instead of α-cyano-4-hydroxycinnamic acid as matrix in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for analyses of in-gel digests of silver-stained proteins: in Analytical Biochemistry(ISSN 0003-2697), vol 371, issue 1, pp 121-1232007In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 371, no 1, p. 121-123Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 5.
    Helmfrid, Ingela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Nosratabadi, Ali Reza
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Augustsson, Anna
    Linnaeus University, Kalmar, Sweden.
    Filipsson, Monika
    Linnaeus University, Kalmar, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Berglund, Marika
    Karolinska Institutet, Stockholm, Sweden.
    Exposure of metals and PAH through local foods and risk of cancer in a historically contaminated glasswork area2019In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 131, article id UNSP 104985Article in journal (Refereed)
    Abstract [en]

    Background

    Production of crystal glass and colored art glassware have been going on in the south-eastern part of Sweden since the 1700s, at over 100 glassworks and smaller glass blowing facilities, resulting in environmental contamination with mainly arsenic (As), cadmium (Cd), lead (Pb) and polycyclic hydrocarbons (PAH). High levels of metals have been found in soil, and moderately elevated levels in vegetables, mushrooms and berries collected around the glassworks sites compared with reference areas. Food in general, is the major exposure source to metals, such as Cd and Pb, and PAHs. Exposure to these toxic metals and PAH has been associated with a variety of adverse health effects in humans including cancer.

    Objective

    The aim of the present study was to evaluate the occurrence of cancer in a cohort from the contaminated glasswork area in relation to long-term dietary intake of locally produced foods, while taking into account residential, occupational and life styles factors.

    Methods

    The study population was extracted from a population cohort of 34,266 individuals who, at some time between the years 1979–2004, lived within a 2 km radius of a glassworks or glass landfill. Register information on cancer incidence and questionnaire information on consumption of local foods (reflecting 30 years general eating habits), life-time residence in the area, life style factors and occupational exposure was collected. Furthermore, blood (n = 660) and urine (n = 400) samples were collected in a subsample of the population to explore associations between local food consumption frequencies, biomarker concentrations in blood (Cd, Pb, As) and urine (PAH metabolite 1-OHPy) as well as environmental and lifestyle factors. The concurrent exposure to persistent organic pollutants (POPs) from food was also considered. A case-control study was performed for evaluation of associations between intakes of local food and risk of cancer.

    Results

    Despite high environmental levels of Cd, Pb and As at glasswork sites and landfills, current metal exposure in the population living in the surrounding areas was similar or only moderately higher in our study population compared to the general population. Reported high consumption of certain local foods was associated with higher Cd and Pb, but not As, concentrations in blood, and 1-OHPy in urine. An increased risk of cancer was associated with smoking, family history of cancer, obesity, and residence in glasswork area before age 5 years. Also, a long-term high consumption of local foods (reflecting 30 years general eating habits), i.e. fish and meat (game, chicken, lamb), was associated with increased risk of various cancer forms.

    Conclusions

    The associations between consumption of local food and different types of cancer may reflect a higher contaminant exposure in the past, and thus, if consumption of local food contributes to the risk of acquiring cancer, that contribution is probably lower today than before. Furthermore, it cannot be ruled out that other contaminants in the food contribute to the increased cancer risks observed.

  • 6.
    Holleboom, Adriaan G
    et al.
    Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Lin, Ruei-Shiuan
    Section on Biological Chemistry, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
    Beres, Thomas M
    Section on Biological Chemistry, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
    Sierts, Jeroen A
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Herman, Daniel S
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
    Stroes, Erik S G
    Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Aerts, Johannes M
    Department of Medical Biochemistry, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Kastelein, John J P
    Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Motazacker, Mohammad M
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Dallinga-Thie, Geesje M
    Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Levels, Johannes H M
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Zwinderman, Aeilko H
    Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Seidman, Jonathan G
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
    Seidman, Christine E
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lefeber, Dirk J
    Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen 6525GA, The Netherlands.
    Morava, Eva
    Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Center, Nijmegen 6525GA, The Netherlands.
    Wevers, Ron A
    Department of Laboratory Medicine, Radboud University Nijmegen Medical Center, Nijmegen 6525GA, The Netherlands.
    Fritz, Timothy A
    Food and Drug Administration, Rockville, MD 20852, USA.
    Tabak, Lawrence A
    Section on Biological Chemistry, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Hovingh, G Kees
    Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Kuivenhoven, Jan Albert
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Heterozygosity for a Loss-of-Function Mutation in GALNT2 Improves Plasma Triglyceride Clearance in Man2011In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 14, no 6, p. 811-8Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies have identified GALNT2 as a candidate gene in lipid metabolism, but it is not known how the encoded enzyme ppGalNAc-T2, which contributes to the initiation of mucin-type O-linked glycosylation, mediates this effect. In two probands with elevated plasma high-density lipoprotein cholesterol and reduced triglycerides, we identified a mutation in GALNT2. It is shown that carriers have improved postprandial triglyceride clearance, which is likely attributable to attenuated glycosylation of apolipoprotein (apo) C-III, as observed in their plasma. This protein inhibits lipoprotein lipase (LPL), which hydrolyses plasma triglycerides. We show that an apoC-III-based peptide is a substrate for ppGalNAc-T2 while its glycosylation by the mutant enzyme is impaired. In addition, neuraminidase treatment of apoC-III which removes the sialic acids from its glycan chain decreases its potential to inhibit LPL. Combined, these data suggest that ppGalNAc-T2 can affect lipid metabolism through apoC-III glycosylation, thereby establishing GALNT2 as a lipid-modifying gene.

  • 7.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Lipoproteomics: A New Approach to the Identification and Characterization of Proteins in LDL and HDL2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A proteomic approach was applied to examine the protein composition of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in humans. LDL and HDL were isolated by density gradient ultracentrifugation, and proteins were separated with twodimensional gel electrophoresis (2-DE) and identified with peptide mass fingerprinting, using matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and with amino acid sequencing using electrospray ionization tandem mass spectrometry. To improve the identification of low abundant proteins in silver stained 2-DE gels, 2,5-dihydroxybenzoic acid was used instead of α-cyano-4-hydroxycinnamic acid as matrix in the peptide mass fingerprinting procedure; this was demonstrated to give more matching peptide peaks, higher sequence coverage, and higher signal to noise ratio. Altogether 18 different proteins were demonstrated in LDL and/or HDL: three of these (calgranulin A, lysozyme C and transthyretin) have not been identified in LDL before. Apo C-II, apo C-III, apo E, apo A-I, apo A-IV, apo J, apo M, serum amyloid A-IV and α1-antitrypsin were found in both LDL and HDL, while apo B-100 (clone), calgranulin A, lysozyme C and transthyretin were found only in LDL, and apo A-II, apo C-I, and serum amyloid A only in HDL. Salivary α-amylase wass identified only in HDL2, and apo L and glycosylated apo A-II only in HDL3. Many of the proteins occurred in a number of isoforms: in all, 47 different isoform identities were demonstrated. A 2-DE mobility shift assay and deglycosylation experiments were used to demonstrate, for the first time, that apo M in LDL and HDL occurs in five isoforms; three that are both N-glycosylated and sialylated, one that is N-glycosylated but not sialylated and one that is neither N-glycosylated nor sialylated. LDL from obese subjects was found to contain more apo J, apo C-II, apo M, α1-antitrypsin and serum amyloid A-IV than LDL from controls,, and also more of an acidic isoform (pI/Mr; 5.2 / 23 100) of apo A-I. In addition, the new LDLassociated protein transthyretin, was found to be significantly more abundant in LDL from obese subjects. On the other hand, the amounts of apo A-IV and the major isoform of apo A-I (pI/Mr; 5.3 / 23 100) were significantly less. Altogether, these findings (i) illustrate the power of 2-DE and mass spectrometry for detailed mapping of the proteins and their isoforms in human lipoproteins; (ii) demonstrate the presence of a number of new proteins in LDL (calgranulin A, lysozyme C and transthyretin); (iii) give precise biochemical clues to the polymorphism of apo M in LDL and HDL, and; (iv) indicate that obesity is associated with significant changes in the protein profile of LDL. It is concluded that new information on lipoproteins can easily be obtained through a proteomic approach, thus facilitating the development of a new proteomic field: lipoproteomics. Much further investigation in this field is warranted, particularly because newly discovered LDL and HDL proteins may play hitherto unknown role(s) in inflammatory reactions of the arterial wall and evolve as useful biomarkers in cardiovascular disease.

    List of papers
    1. Lipoproteomics I: Mapping of proteins in low-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry
    Open this publication in new window or tab >>Lipoproteomics I: Mapping of proteins in low-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry
    2005 (English)In: Proteomics, ISSN 1615-9853, Vol. 5, no 2, p. 551-565Article in journal (Refereed) Published
    Abstract [en]

    The molecular mechanisms underlying the relationship between low-density lipoprotein (LDL) and the risk of atherosclerosis are not clear. Therefore, detailed information about the protein composition of LDL may contribute to reveal its role in atherogenesis and the mechanisms that lead to coronary disease in humans. Here, we sought to map the proteins in human LDL by a proteomic approach. LDL was isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix assisted laser desorption/ionization-time of flight-mass spectrometry and with amino acid sequencing using electrospray ionization tandem mass spectrometry. These procedures identified apo B-100, apo C-II, apo C-III (three isoforms), apo E (four isoforms), apo A-I (two isoforms), apo A-IV, apo J and apo M (three isoforms not previously described). In addition, three proteins that have not previously been identified in LDL were found: serum amyloid A-IV (two isoforms), calgranulin A, and lysozyme C. The identities of apo M, calgranulin A, and lysozyme C were confirmed by sequence information obtained after collision-induced dissociation fragmentation of peptides characteristic for these proteins. Moreover, the presence of lysozyme C was further corroborated by demonstrating enriched hydrolytic activity in LDL against Micrococcus lysodeikticus. These results indicate that in addition to the dominating apo B-100, LDL contains a number of other apolipoproteins, many of which occur in different isoforms. The demonstration, for the first time, that LDL contains calgranulin A and lysozyme C raises the possibility that LDL proteins may play hitherto unknown role(s) in immune and inflammatory reactions of the arterial wall.

    Keywords
    Low-density lipoprotein, Lysozyme, Matrix assisted laser desorption/ionization-time of flight-mass spectrometry, Tandem mass spectrometry, Two-dimensional gel electrophoresis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14350 (URN)10.1002/pmic.200300938 (DOI)
    Available from: 2007-03-15 Created: 2007-03-15 Last updated: 2013-09-20
    2. Lipoproteomics II: Mapping of proteins in high-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry
    Open this publication in new window or tab >>Lipoproteomics II: Mapping of proteins in high-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry
    2005 (English)In: Proteomics, ISSN 1615-9853, Vol. 5, no 5, p. 1431-1445Article in journal (Refereed) Published
    Abstract [en]

    High-density lipoprotein (HDL) is the most abundant lipoprotein particle in the plasma and a negative risk factor of atherosclerosis. By using a proteomic approach it is possible to obtain detailed information about its protein content and protein modifications that may give new information about the physiological roles of HDL. In this study the two subfractions; HDL2 and HDL3, were isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix-assisted laser desorption/ionisation time of flight mass spectrometry. Identified proteins in HDL were: the dominating apo A-I as six isoforms, four of them with a glycosylation pattern and one of them with retained propeptide, apolipoprotein (apo) A-II, apo A-IV, apo C-I, apo C-II, apo C-III (two isoforms), apo E (five isoforms), the recently discovered apo M (two isoforms), serum amyloid A (two isoforms) and serum amyloid A-IV (six isoforms). Furthermore, alpha-1-antitrypsin was identified in HDL for the first time. Additionally, salivary alpha-amylase was identified as two isoforms in HDL2, and apo L and a glycosylated apo A-II were identified in HDL3. Besides confirming the presence of different apolipoproteins, this study indicates new patterns of glycosylated apo A-I and apo A-II. Furthermore, the study reveals new proteins in HDL; alpha-1-antitrypsin and salivary alpha-amylase. Further investigations about these proteins may give new insight into the functional role of HDL in coronary artery diseases.

    Keywords
    High-density lipoprotein, Matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry, Two-dimensional gel electrophoresis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14351 (URN)10.1002/pmic.200401010 (DOI)
    Available from: 2007-03-15 Created: 2007-03-15 Last updated: 2013-09-20
    3. Peptide mass fingerprint data from silver stained proteins can be improved by using 2,5-dihydroxybenzoic acid instead of α-cyano-4-hydroxycinnamic acid as matrix in MALDI-TOF MS
    Open this publication in new window or tab >>Peptide mass fingerprint data from silver stained proteins can be improved by using 2,5-dihydroxybenzoic acid instead of α-cyano-4-hydroxycinnamic acid as matrix in MALDI-TOF MS
    Show others...
    2007 (English)Article in journal (Refereed) Submitted
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14352 (URN)
    Available from: 2007-03-15 Created: 2007-03-15
    4. Characterization of apolipoprotein M isoforms in low-density lipoprotein
    Open this publication in new window or tab >>Characterization of apolipoprotein M isoforms in low-density lipoprotein
    2006 (English)In: Journal of proteome research, ISSN 1535-3893, Vol. 5, no 10, p. 2685-2690Article in journal (Refereed) Published
    Abstract [en]

    Apo M is a recently discovered human lipoprotein thought to be involved in the metabolism of lipids and lipoprotein particles. Here, a proteomic approach was applied to examine the glycosylation pattern of apo M in human LDL. We treated LDL proteins with N-glycosidase or neuraminidase, studied mobility shifts of Apo M by two-dimensional gel electrophoresis, and different isoforms were then identified with mass spectrometry. This way, we demonstrated the presence of five isoforms of apo M in LDL:  three that are both N-glycosylated and sialylated, one that is N-glycosylated but not sialylated, and one that is neither N-glycosylated nor sialylated. As judged from the examination of LDL from 20 healthy human subjects, the three N-glycosylated and sialylated forms are most abundant (80−100% of the total apo M in LDL) whereas the unsialylated and unglycosylated variants constitute at most 20%. Comparative analysis showed that the same five isoforms of apo M are also present in HDL. Further studies aiming at elucidating the role of apo M in health and disease will have to take this polymorphism of apo M proteins into account.

    Keywords
    apolipoprotein M, apo M, low-density lipoprotein, LDL, two-dimensional gel electrophoresis, 2-DE, MALDI-TOF mass spectrometry, glycosylations, sialylations
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14353 (URN)10.1021/pr060180x (DOI)
    Available from: 2007-03-15 Created: 2007-03-15
    5. Comparative proteomics of lowdensity lipoprotein from normal weight and obese adults
    Open this publication in new window or tab >>Comparative proteomics of lowdensity lipoprotein from normal weight and obese adults
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-14354 (URN)
    Available from: 2007-03-15 Created: 2007-03-15 Last updated: 2010-01-13
  • 8.
    Karlsson, Helen
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lipoproteomics: mapping of proteins in LDL and HDL2005Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    High-density lipoprotein (HDL) and (LDL)-density lipoprotein (LDL) are important lipoprotein fractions in human plasma. HDL is the most abundant lipoprotein particle and a negative risk factor of atherosclerosis while LDL is considered to possess atherogenic properties. The molecular mechanisms underlying the relationship between LDU/HDL and the development of atherosclerosis are not clear. Therefore, detailed information about the protein composition of LDU/HDL may contribute to reveal their role in atherogenesis and the mechanisms that lead to or protect from coronary disease in humans. Here, we sought to map the proteins in human LDL/HDL by a proteomic approach.

    LDL and HDL were isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix assisted laser desorption/ionization-time of flight-mass spectrometry and with amino acid sequencing using electrospray ionization tandem mass spectrometry.

    In LDL these procedures identified apo B-100, apo C-II, apo C-I (three isoforms), apo E (four isoforms), apo A-I (three isoforms), apo A-IV, apo J and apo M (three isoforms not previously described). In addition, three proteins that have not previously been identified in LDL were found: serum amyloid A-IV (two isoforms). calgranulin A and lysozyme C. The identities of apo M, calgranulin A, and lysozyme C were confirmed by sequence information obtained after collision-induced dissociation fragmentation of pep tides characteristic for these proteins. Moreover, the presence of lysozyme C was further corroborated by demonstrating enriched hydrolytic activity in LDL against Micrococcus lysodeikticus.

    Identified proteins in HDL were: the dominating apo A-1 as seven isoforms, four of them with a modification pattern and one of them with retained propeptide, apo A-II, apo A-IV, apo C-I. apo C-II, apo C-III (two isoforms), apo E (five isoforms), apo J, the recently discovered apo M (two isoforms), serum amyloid A (two isoforms) and serum amyloid A-IV (six isoforms). Furthermore, alpha-1-antitrypsin was identified in HDL for the first time. Additionally, salivary alpha-amylase was identified as two isoforms in HDL2 , and apo L and aglycosylatcd apo A-II were identified in HDL3.

    These results indicate that both LDL and HDL contains a number of apolipoproteins, many of them occurs in different isoforms. The demonstration, for the first time, that LDL contains calgranulin A, lysozyme C and apo J raises the possibility that LDL proteins may play hitherto unknown role(s) in immune and inflammatory reactions of the arterial wall. Additionally, new patterns of glycosylated apo A-I and apo A-II and new proteins; alpha-1-antitrypsin and salivary alpha-amylase were detected in HDL. Further investigations about these proteins may give new insight into the functional role of LDL and HDL in coronary artery disease.

    List of papers
    1. Lipoproteomics I: Mapping of proteins in low-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry
    Open this publication in new window or tab >>Lipoproteomics I: Mapping of proteins in low-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry
    2005 (English)In: Proteomics, ISSN 1615-9853, Vol. 5, no 2, p. 551-565Article in journal (Refereed) Published
    Abstract [en]

    The molecular mechanisms underlying the relationship between low-density lipoprotein (LDL) and the risk of atherosclerosis are not clear. Therefore, detailed information about the protein composition of LDL may contribute to reveal its role in atherogenesis and the mechanisms that lead to coronary disease in humans. Here, we sought to map the proteins in human LDL by a proteomic approach. LDL was isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix assisted laser desorption/ionization-time of flight-mass spectrometry and with amino acid sequencing using electrospray ionization tandem mass spectrometry. These procedures identified apo B-100, apo C-II, apo C-III (three isoforms), apo E (four isoforms), apo A-I (two isoforms), apo A-IV, apo J and apo M (three isoforms not previously described). In addition, three proteins that have not previously been identified in LDL were found: serum amyloid A-IV (two isoforms), calgranulin A, and lysozyme C. The identities of apo M, calgranulin A, and lysozyme C were confirmed by sequence information obtained after collision-induced dissociation fragmentation of peptides characteristic for these proteins. Moreover, the presence of lysozyme C was further corroborated by demonstrating enriched hydrolytic activity in LDL against Micrococcus lysodeikticus. These results indicate that in addition to the dominating apo B-100, LDL contains a number of other apolipoproteins, many of which occur in different isoforms. The demonstration, for the first time, that LDL contains calgranulin A and lysozyme C raises the possibility that LDL proteins may play hitherto unknown role(s) in immune and inflammatory reactions of the arterial wall.

    Keywords
    Low-density lipoprotein, Lysozyme, Matrix assisted laser desorption/ionization-time of flight-mass spectrometry, Tandem mass spectrometry, Two-dimensional gel electrophoresis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14350 (URN)10.1002/pmic.200300938 (DOI)
    Available from: 2007-03-15 Created: 2007-03-15 Last updated: 2013-09-20
    2. Lipoproteomics II: Mapping of proteins in high-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry
    Open this publication in new window or tab >>Lipoproteomics II: Mapping of proteins in high-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry
    2005 (English)In: Proteomics, ISSN 1615-9853, Vol. 5, no 5, p. 1431-1445Article in journal (Refereed) Published
    Abstract [en]

    High-density lipoprotein (HDL) is the most abundant lipoprotein particle in the plasma and a negative risk factor of atherosclerosis. By using a proteomic approach it is possible to obtain detailed information about its protein content and protein modifications that may give new information about the physiological roles of HDL. In this study the two subfractions; HDL2 and HDL3, were isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix-assisted laser desorption/ionisation time of flight mass spectrometry. Identified proteins in HDL were: the dominating apo A-I as six isoforms, four of them with a glycosylation pattern and one of them with retained propeptide, apolipoprotein (apo) A-II, apo A-IV, apo C-I, apo C-II, apo C-III (two isoforms), apo E (five isoforms), the recently discovered apo M (two isoforms), serum amyloid A (two isoforms) and serum amyloid A-IV (six isoforms). Furthermore, alpha-1-antitrypsin was identified in HDL for the first time. Additionally, salivary alpha-amylase was identified as two isoforms in HDL2, and apo L and a glycosylated apo A-II were identified in HDL3. Besides confirming the presence of different apolipoproteins, this study indicates new patterns of glycosylated apo A-I and apo A-II. Furthermore, the study reveals new proteins in HDL; alpha-1-antitrypsin and salivary alpha-amylase. Further investigations about these proteins may give new insight into the functional role of HDL in coronary artery diseases.

    Keywords
    High-density lipoprotein, Matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry, Two-dimensional gel electrophoresis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14351 (URN)10.1002/pmic.200401010 (DOI)
    Available from: 2007-03-15 Created: 2007-03-15 Last updated: 2013-09-20
  • 9.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Chroni, Angeliki
    Institute of Biology, National Center for Scientific Research, Demokritos, Athens, Greece.
    George, Leondaritis
    Institute of Biology, National Center for Scientific Research, Demokritos, Athens, Greece.
    Lipids and Lipoproteins in Atherosclerosis / Special issue2011In: Journal of Lipids, ISSN 2090-3030, E-ISSN 2090-3049Article in journal (Refereed)
    Abstract [en]

    Atherosclerosis is a focal disease of the arterial wall that leads to cardiovascular disease (CVD), the biggest cause of morbidity and mortality in Western societies. Atherosclerosis is a complex, chronic, progressive disease that affects large and medium-sized arteries. Atherosclerotic lesions are promoted by low-density lipoproteins and form from accumulation of fatty substances, cholesterol, cellular waste products, calcium, and fibrin in the inner lining of the arterial wall. Lipoproteins are complexes of amphipathic proteins with lipids at variable ratios, densities, and sizes. Their role is to transport water-insoluble lipids in the blood. Plasma lipoproteins have traditionally been grouped into five major classes, based on their buoyant density: chylomicrons, very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). It is believed that atherogenic lipoproteins, such as LDL and lipoprotein remnants, that float in the VLDL IDL region, promote atherosclerosis, and antiatherogenic lipoproteins, such as HDL, protect from atherosclerosis. Despite many advances in cardiology, atherosclerosis remains an important medical problem suggesting that some steps in pathogenic mechanisms remain unclear.

    This special issue contains a series of reviews and original research articles that seek to provide insight into the role of lipids and lipoproteins in health and disease with emphasis given on their implication in atherosclerosis.

  • 10.
    Karlsson, Helen
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Ghafouri, Bijar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Leanderson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Kartläggning av proteiner i LDL och HDL med två-dimensionell gelelektrofores samt masspektrometri.2003In: Svenska Läkaresällskapets Handlingar,2003, 2003, p. 11-26Conference paper (Refereed)
  • 11.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Kontush, Anatol
    University of Pierre and Marie Curie, Paris, France .
    James, Richard W
    University of Geneva, Geneva, Switzerland .
    Functionality of HDL: Antioxidation and Detoxifying Effects.2015In: Handbook of Experimental Pharmacology, ISSN 0171-2004, E-ISSN 1865-0325, Vol. 224, p. 207-28Article in journal (Refereed)
    Abstract [en]

    High-density lipoproteins (HDL) are complexes of multiple talents, some of which have only recently been recognised but all of which are under active investigation. Clinical interest initially arose from their amply demonstrated role in atherosclerotic disease with their consequent designation as a major cardiovascular disease (CVD) risk factor. However, interest is no longer confined to vascular tissues, with the reports of impacts of the lipoprotein on pancreatic, renal and nervous tissues, amongst other possible targets. The ever-widening scope of HDL talents also encompasses environmental hazards, including infectious agents and environmental toxins. In almost all cases, HDL would appear to have a beneficial impact on health. It raises the intriguing question of whether these various talents emanate from a basic ancestral function to protect the cell.The following chapter will illustrate and review our current understanding of some of the functions attributed to HDL. The first section will look at the antioxidative functions of HDL and possible mechanisms that are involved. The second section will focus specifically on paraoxonase-1 (PON1), which appears to bridge the divide between the two HDL functions discussed herein. This will lead into the final section dealing with HDL as a detoxifying agent protecting against exposure to environmental pathogens and other toxins.

  • 12.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lipoproteomics I: Mapping of proteins in low-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry2005In: Proteomics, ISSN 1615-9853, Vol. 5, no 2, p. 551-565Article in journal (Refereed)
    Abstract [en]

    The molecular mechanisms underlying the relationship between low-density lipoprotein (LDL) and the risk of atherosclerosis are not clear. Therefore, detailed information about the protein composition of LDL may contribute to reveal its role in atherogenesis and the mechanisms that lead to coronary disease in humans. Here, we sought to map the proteins in human LDL by a proteomic approach. LDL was isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix assisted laser desorption/ionization-time of flight-mass spectrometry and with amino acid sequencing using electrospray ionization tandem mass spectrometry. These procedures identified apo B-100, apo C-II, apo C-III (three isoforms), apo E (four isoforms), apo A-I (two isoforms), apo A-IV, apo J and apo M (three isoforms not previously described). In addition, three proteins that have not previously been identified in LDL were found: serum amyloid A-IV (two isoforms), calgranulin A, and lysozyme C. The identities of apo M, calgranulin A, and lysozyme C were confirmed by sequence information obtained after collision-induced dissociation fragmentation of peptides characteristic for these proteins. Moreover, the presence of lysozyme C was further corroborated by demonstrating enriched hydrolytic activity in LDL against Micrococcus lysodeikticus. These results indicate that in addition to the dominating apo B-100, LDL contains a number of other apolipoproteins, many of which occur in different isoforms. The demonstration, for the first time, that LDL contains calgranulin A and lysozyme C raises the possibility that LDL proteins may play hitherto unknown role(s) in immune and inflammatory reactions of the arterial wall.

  • 13.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lipoproteomics II: Mapping of proteins in high-density lipoprotein using two-dimensional gel electrophoresis and mass spectrometry2005In: Proteomics, ISSN 1615-9853, Vol. 5, no 5, p. 1431-1445Article in journal (Refereed)
    Abstract [en]

    High-density lipoprotein (HDL) is the most abundant lipoprotein particle in the plasma and a negative risk factor of atherosclerosis. By using a proteomic approach it is possible to obtain detailed information about its protein content and protein modifications that may give new information about the physiological roles of HDL. In this study the two subfractions; HDL2 and HDL3, were isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix-assisted laser desorption/ionisation time of flight mass spectrometry. Identified proteins in HDL were: the dominating apo A-I as six isoforms, four of them with a glycosylation pattern and one of them with retained propeptide, apolipoprotein (apo) A-II, apo A-IV, apo C-I, apo C-II, apo C-III (two isoforms), apo E (five isoforms), the recently discovered apo M (two isoforms), serum amyloid A (two isoforms) and serum amyloid A-IV (six isoforms). Furthermore, alpha-1-antitrypsin was identified in HDL for the first time. Additionally, salivary alpha-amylase was identified as two isoforms in HDL2, and apo L and a glycosylated apo A-II were identified in HDL3. Besides confirming the presence of different apolipoproteins, this study indicates new patterns of glycosylated apo A-I and apo A-II. Furthermore, the study reveals new proteins in HDL; alpha-1-antitrypsin and salivary alpha-amylase. Further investigations about these proteins may give new insight into the functional role of HDL in coronary artery diseases.

  • 14.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lindbom, John
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Gustafsson, Mats
    Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Ljungman, Anders G
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Wear Particles from Studded Tires and Granite Pavement Induce Pro-inflammatory Alterations in Human Monocyte-Derived Macrophages: A Proteomic Study.2011In: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 24, p. 45-53Article in journal (Refereed)
    Abstract [en]

    Airborne particulate matter is considered to be one of the environmental contributors to the mortality in cancer, respiratory, and cardiovascular diseases. For future preventive actions, it is of major concern to investigate the toxicity of defined groups of airborne particles and to clarify their pathways in biological tissues. To expand the knowledge beyond general inflammatory markers, this study examined the toxicoproteomic effects on human monocyte derived macrophages after exposure to wear particles generated from the interface of studded tires and a granite-containing pavement. As comparison, the effect of endotoxin was also investigated. The macrophage proteome was separated using two-dimensional gel electrophoresis. Detected proteins were quantified, and selected proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Among analyzed proteins, seven were significantly decreased and three were increased by exposure to wear particles as compared to unexposed control cells. Endotoxin exposure resulted in significant changes in the expression of six proteins: four decreased and two increased. For example, macrophage capping protein was significantly increased after wear particle exposure only, whereas calgizzarin and galectin-3 were increased by both wear particle and endotoxin exposure. Overall, proteins associated with inflammatory response were increased and proteins involved in cellular functions such as redox balance, anti-inflammatory response, and glycolysis were decreased. Investigating the effects of characterized wear particles on human macrophages with a toxicoproteomic approach has shown to be useful in the search for more detailed information about specific pathways and possible biological markers.

  • 15.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lindqvist, Helen
    Department of Chemistry and Bioscience/Food Science, Chalmers University of Technology, Göteborg, Sweden.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Characterization of apolipoprotein M isoforms in low-density lipoprotein2006In: Journal of proteome research, ISSN 1535-3893, Vol. 5, no 10, p. 2685-2690Article in journal (Refereed)
    Abstract [en]

    Apo M is a recently discovered human lipoprotein thought to be involved in the metabolism of lipids and lipoprotein particles. Here, a proteomic approach was applied to examine the glycosylation pattern of apo M in human LDL. We treated LDL proteins with N-glycosidase or neuraminidase, studied mobility shifts of Apo M by two-dimensional gel electrophoresis, and different isoforms were then identified with mass spectrometry. This way, we demonstrated the presence of five isoforms of apo M in LDL:  three that are both N-glycosylated and sialylated, one that is N-glycosylated but not sialylated, and one that is neither N-glycosylated nor sialylated. As judged from the examination of LDL from 20 healthy human subjects, the three N-glycosylated and sialylated forms are most abundant (80−100% of the total apo M in LDL) whereas the unsialylated and unglycosylated variants constitute at most 20%. Comparative analysis showed that the same five isoforms of apo M are also present in HDL. Further studies aiming at elucidating the role of apo M in health and disease will have to take this polymorphism of apo M proteins into account.

  • 16.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ahrén, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ljungman, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Two-dimensional gel electrophoresis and mass spectrometry in studies of nanoparticle-protein interactions2012In: Gel electrophoresis-Advanced Techniques / [ed] Sameh Magdeldin, Rijeka, Croatia: In Tech , 2012, p. 1-32Chapter in book (Other academic)
    Abstract [en]

    Over the years a number of epidemiological studies have shown that PM from combustion sources such as motor vehicles contributes to respiratory and cardiovascular morbidity and mortality.Especially so do the ultra-fine particles (UFPs) with a diameter less than 0.1 micrometer.UFPs from combustion engines are capable to translocate over the alveolar–capillary barrier.  When nano-sized PM (nanoparticles, NP), which are small enough to enter the blood stream, do so they are likely to interact with plasma proteins and this protein-NP interaction will probably affect the fate of and the effects caused by the NPs in the human body. Here, by using a proteomic approach, we present results showing that several proteins indeed are associated to NPs that have in vitro been introduced to human blood plasma.

  • 17.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre. Östergötlands Läns Landsting, Centre for Medicine.
    Mortstedt, Harriet
    n/a.
    Lindqvist, Helen
    Chalmers.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Protein profiling of low-density lipoprotein from obese subjects2009In: PROTEOMICS CLINICAL APPLICATIONS, ISSN 1862-8346, Vol. 3, no 6, p. 663-671Article in journal (Refereed)
    Abstract [en]

    Although obesity and high levels of low-density lipoprotein (LDL) are well-known risk factors for cardiovascular disease, the precise role(s) of different LDL constituents in obesity has not been explored. In the present study, we compared the LDL proteome of healthy control adults (body mass index less than 25) and obese subjects (body mass index greater than 30). LDL was isolated by density-gradient ultracentrifugation and proteins were separated with 2-D PAGE, quantified, and identified by peptide mass fingerprinting using MALDI-TOF MS. A new LDL-associated protein was identified as transthyretin and found to be significantly more abundant in LDL from the obese subjects. In addition, LDL from the obese subjects contained relatively more alpha(1)-antitrypsin, apo J, apo C-II, than LDL from controls, and also more of an acidic isoform (pI/Mr; 5.2/23 100) of apo A-I. On the other hand, the relative amounts of apo A-IV and the major isoform of apo A-I (pI/Mr; 5.3/23 100) were significantly less in LDL from the obese subjects. Apo E was less and non-sialylated apo C-III more abundant in LDL from obese men than control men, while there were no such differences between LDL from obese and control women. These findings illustrate that obesity is not only associated with increased LDL-cholesterol levels but also with alterations in the LDL protein composition. The presence of transthyretin in LDL from obese subjects may reflect over-nutrition and affect the lipid metabolism in obesity.

  • 18.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre. Östergötlands Läns Landsting.
    Sundberg, Sofie
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Levels, J H M
    Acad Med Centre, Amsterdam, Netherlands .
    Turkina, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Daniel, G
    National Centre for Science Research Demokritos.
    Chroni, A
    National Centre for Science Research Demokritos.
    Kuivenhoven, J A
    Acad Med Centre, Amsterdam, Netherlands .
    Hovingh, G K
    Acad Med Centre, Amsterdam, Netherlands.
    Holleboom, A G
    Acad Med Centre, Amsterdam, Netherlands.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    MUTANT apo A-I (L178P) IDENTIFIED IN HDL FROM HETEROZYGOTES OF A FAMILY WITH ENDOTHELIAL DYSFUNCTION AND INCREASED ARTERIAL WALL THICKNESS in ATHEROSCLEROSIS SUPPLEMENTS, vol 11, issue 2, pp 67-672010In: ATHEROSCLEROSIS SUPPLEMENTS, Elsevier Science B.V., Amsterdam. , 2010, Vol. 11, no 2, p. 67-67Conference paper (Refereed)
    Abstract [en]

    n/a

  • 19.
    Levels, Johannes HM
    et al.
    Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    Geurts, Pierre
    Department of Electrical Engineering and Computer Science & GIGA-research, University of Liège, Belgium.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Marée, Raphaël
    GIGA Bioinformatics Platform, University of Liège, Belgium.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Fornander, Louise
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Wehenkel, Louis
    Department of Electrical Engineering and Computer Science & GIGA-research, University of Liège, Belgium.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Stroes, Erik SG
    Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    Kuivenhoven, Jan A
    Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    Meijers, Joost CM
    Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    High-density Lipoprotein proteome dynamics in human endotoxemia2011In: Proteome Science, ISSN 1477-5956, E-ISSN 1477-5956, Vol. 9, no 34Article in journal (Refereed)
    Abstract [en]

    Background: A large variety of proteins involved in inflammation, coagulation, lipid-oxidation and lipid metabolism have been associated with high-density lipoprotein (HDL) and it is anticipated that changes in the HDL proteome have implications for the multiple functions of HDL. Here, SELDI-TOF mass spectrometry (MS) was used to study the dynamic changes of HDL protein composition in a human experimental low-dose endotoxemia model. Ten healthy men with low HDL cholesterol (0.7+/-0.1 mmol/L) and 10 men with high HDL cholesterol levels (1.9+/-0.4mmol/L) were challenged with endotoxin (LPS) intravenously (1ng/kg bodyweight). We previously showed that subjects with low HDL cholesterol are more susceptible to an inflammatory challenge. The current study tested the hypothesis that this discrepancy may be related to differences in the HDL proteome.

    Results: Plasma drawn at 7 time-points over a 24 hour time period after LPS challenge was used for direct capture of HDL using antibodies against apolipoprotein A-I followed by subsequent SELDI-TOF MS profiling. Upon LPS administration, profound changes in 21 markers (adjusted p-value<0.05) were observed in the proteome in both study groups. These changes were observed 1 hour after LPS infusion and sustained up to 24 hours, but unexpectedly were not different between the 2 study groups. Hierarchical clustering of the protein spectra at all time points of all individuals revealed 3 distinct clusters, which were largely independent of baseline HDL cholesterol levels but correlated with paraoxonase 1 activity. The acute phase protein serum amyloid A-1/2 (SAA-1/2) was clearly upregulated after LPS infusion in both groups and comprised both native and N-terminal truncated variants that were identified by two-dimensional gel electrophoresis and mass spectrometry. Individuals of one of the clusters were distinguished by a lower SAA-1/2 response after LPS challenge and a delayed time-response of the truncated variants.

    Conclusions: This study shows that the semi-quantitative differences in the HDL proteome as assessed by SELDI-TOF MS cannot explain why subjects with low HDL cholesterol are more susceptible to a challenge with LPS than those with high HDL cholesterol. Instead the results indicate that hierarchical clustering could be useful to predict HDL functionality in acute phase responses towards LPS.

  • 20.
    Liang, Wenzhao
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Jilin University, Peoples R China.
    Ward, Liam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Wei
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Yuan, Ximing
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Distinctive proteomic profiles among different regions of human carotid plaques in men and women2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 26231Article in journal (Refereed)
    Abstract [en]

    The heterogeneity of atherosclerotic tissue has limited comprehension in proteomic and metabolomic analyses. To elucidate the functional implications, and differences between genders, of atherosclerotic lesion formation we investigated protein profiles from different regions of human carotid atherosclerotic arteries; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Proteomic analysis was performed using 2-DE with MALDI-TOF, with validation using nLC-MS/MS. Protein mapping of 2-DE identified 52 unique proteins, including 15 previously unmapped proteins, of which 41 proteins were confirmed by nLC-MS/MS analysis. Expression levels of 18 proteins were significantly altered in plaque regions compared to the internal control region. Nine proteins showed site-specific alterations, irrespective of gender, with clear associations to extracellular matrix remodelling. Five proteins display gender-specific alterations with 2-DE, with two alterations validated by nLC-MS/MS. Gender differences in ferritin light chain and transthyretin were validated using both techniques. Validation of immunohistochemistry confirmed significantly higher levels of ferritin in plaques from male patients. Proteomic analysis of different plaque regions has reduced the effects of plaque heterogeneity, and significant differences in protein expression are determined in specific regions and between genders. These proteomes have functional implications in plaque progression and are of importance in understanding gender differences in atherosclerosis.

  • 21.
    Ljunggren, Stefan A
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Iggland, Madeleine
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rönn, Monika
    Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Uppsala University, Uppsala, Sweden.
    Lind, P M
    Uppsala University, Uppsala, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Altered heart proteome in fructose-fed Fisher 344 rats exposed to bisphenol A.2016In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 347-349, p. 6-16Article in journal (Refereed)
    Abstract [en]

    Bisphenol A (BPA), is an artificial estrogen initially produced for medical purposes but is today widely used in polycarbonate plastics and epoxy resins. Exposure-related reproductive disorders have been found, but recently it has also been suggested that BPA may be involved in obesity, diabetes, myocardial hypertrophy and myocardial infarction in humans. To mimic a modern lifestyle, female rats were fed with fructose or fructose plus BPA (0.25mg/L drinking water). The myocardial left ventricle proteome of water controls, fructose-fed and fructose-fed plus BPA supplemented rats was explored. The proteome was investigated using nano-liquid chromatography tandem mass spectrometry and two-dimensional gel electrophoresis followed by matrix assisted laser desorption/ionization mass spectrometry identification. In total, 41 proteins were significantly altered by BPA exposure compared to water or fructose controls. Principal component analysis and cellular process enrichment analysis of altered proteins suggested increased fatty acid transport and oxidation, increased ROS generation and altered structural integrity of the myocardial left ventricle in the fructose-fed BPA-exposed rats, indicating unfavorable effects on the myocardium. In conclusion, BPA exposure in the rats induces major alterations in the myocardial proteome.

  • 22.
    Ljunggren, Stefan A
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Helmfrid, Ingela
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Salihovic, Samira
    Örebro University, Sweden.
    van Bavel, Bert
    Örebro University, Sweden.
    Wingren, Gun
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer.2014In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 65, p. 93-9Article in journal (Refereed)
    Abstract [en]

    Persistent organic pollutants (POPs) are lipophilic environmental toxins that have been associated with cardiovascular disease (CVD) and cancer. The aim of this study was to investigate the concentrations of POPs in human high and low/very low-density lipoproteins (HDL and LDL/VLDL) and the possible association with CVD and cancer occurrence in individuals living in a contaminated area. Lipoproteins from 28 individuals (7 healthy controls, 8 subjects with cancer, 13 subjects with CVD) were isolated and the fraction-specific concentration of 20 different POPs was analyzed by high resolution gas chromatography/high resolution mass spectrometry. The activity of Paraoxonase 1 (PON1), an anti-oxidant in HDL, was determined in plasma of these 28 subjects and additional 50 subjects from the same area excluding diseases other than cancer or CVD. Fourteen polychlorinated biphenyls (PCBs) and three organochlorine pesticides were detected, and especially highly chlorinated PCBs were enriched in lipoproteins. Significantly higher concentrations of POPs were found among individuals with CVD or cancer compared to controls. Principal component analyses showed that POP concentrations in HDL were more associated with CVD, while POP concentrations in LDL/VLDL were more associated with cancer. PON1 activity was negatively correlated to sumPCB and a co-variation between decreased arylesterase-activity, increased PCB concentrations and CVD was found. This study shows that POPs are present in lipoproteins and were more abundant in individuals with CVD or cancer compared to healthy controls. The results also indicate that PCB exposure is accompanied by reduced PON1 activity that could impair the HDL function to protect against oxidation.

  • 23.
    Ljunggren, Stefan A
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Levels, Johannes H M
    Academic Medical Centre, Amsterdam, the Netherlands.
    Hovingh, Kees
    Academic Medical Centre, Amsterdam, the Netherlands.
    Holleboom, Adriaan G
    Academic Medical Centre, Amsterdam, the Netherlands.
    Vergeer, Menno
    Academic Medical Centre, Amsterdam, the Netherlands.
    Argyri, Letta
    National Center for Scientific Research "Demokritos", Athens, Greece.
    Gkolfinopoulou, Christina
    National Center for Scientific Research "Demokritos", Athens, Greece.
    Chroni, Angeliki
    National Center for Scientific Research "Demokritos", Athens, Greece.
    Sierts, Jeroen A
    Academic Medical Centre, Amsterdam, the Netherlands.
    Kastelein, John J
    Academic Medical Centre, Amsterdam, the Netherlands.
    Kuivenhoven, Jan Albert
    University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1.2015In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1851, no 12, p. 1587-1595Article in journal (Refereed)
    Abstract [en]

    The scavenger receptor class B type 1 (SR-B1) is an important HDL receptor involved in cholesterol uptake and efflux, but its physiological role in human lipoprotein metabolism is not fully understood. Heterozygous carriers of the SR-B1P297S mutation are characterized by increased HDL cholesterol levels, impaired cholesterol efflux from macrophages and attenuated adrenal function. Here, the composition and function of lipoproteins were studied in SR-B1P297S heterozygotes.

    Lipoproteins from six SR-B1P297S carriers and six family controls were investigated. HDL and LDL/VLDL were isolated by ultracentrifugation and proteins were separated by two-dimensional gel electrophoresis and identified by mass spectrometry. HDL antioxidant properties, paraoxonase 1 activities, apoA-I methionine oxidations and HDL cholesterol efflux capacity were assessed.

    Multivariate modeling separated carriers from controls based on lipoprotein composition. Protein analyses showed a significant enrichment of apoE in LDL/VLDL and of apoL-1 in HDL from heterozygotes compared to controls. The relative distribution of plasma apoE was increased in LDL and in lipid-free form. There were no significant differences in paraoxonase 1 activities, HDL antioxidant properties or HDL cholesterol efflux capacity but heterozygotes showed a significant increase of oxidized methionines in apoA-I.

    The SR-B1P297S mutation affects both HDL and LDL/VLDL protein compositions. The increase of apoE in carriers suggests a compensatory mechanism for attenuated SR-B1 mediated cholesterol uptake by HDL. Increased methionine oxidation may affect HDL function by reducing apoA-I binding to its targets. The results illustrate the complexity of lipoprotein metabolism that has to be taken into account in future therapeutic strategies aiming at targeting SR-B1.

  • 24.
    Ljunggren, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Bengtsson, Torbjorn
    Orebro Univ, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Starkhammar Johansson, Carin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Public Dental Health Care.
    Palm, Eleonor
    Orebro Univ, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Davies, Julia
    Malmo Univ, Sweden.
    Svensater, Gunnel
    Malmo Univ, Sweden.
    Lönn, Johanna
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences. Orebro Univ, Sweden; Malmo Univ, Sweden.
    Modified lipoproteins in periodontitis: a link to cardiovascular disease?2019In: Bioscience Reports, ISSN 0144-8463, E-ISSN 1573-4935, Vol. 39, no 3, article id BSR20181665Article in journal (Refereed)
    Abstract [en]

    There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesise that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, the present study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient ultracentrifugation. Proteins were separated by 2D gel-electrophoresis and identified by map-matching or by nano-LC followed by MS. Apolipoprotein (Apo) A-I (ApoA-I) methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed. Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of alpha-1-antichymotrypsin, apoA-II, apoC-III were found in high-density lipoprotein (HDL) from the patients. In low-density lipoprotein (LDL)/very LDL (VLDL), the levels of apoL-1 and platelet-activating factor acetylhydrolase (PAF-AH) as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. alpha-1 antitrypsin and alpha-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. A total of 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2. Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as post-translational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).

  • 25.
    Ljunggren, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Mörtstedt, Harriet
    Occupational and Environmental Medicine, Lund University Hospital, Lund.
    Hellström, L.
    Internal Medicine and Environmental Medicine and Public Health, Oskarshamn Hospital, Oskarshamn, Sweden.
    Perk, J.
    Internal Medicine and Environmental Medicine and Public Health, Oskarshamn Hospital, Oskarshamn, Sweden.
    Besler, C.
    Cardiovascular Center, Zurich University Hospital, Switzerland.
    Landmesser, U.
    Cardiovascular Center, Zurich University Hospital, Switzerland.
    von Eckardstein, A.
    Institute for Clinical Chemistry, Zurich University Hospital, Zurich, Switzerland.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Changes in Human Liportein Composition in Patients with Acute Coronary Syndrome2011In: Atherosclerosis Supplements, ISSN 1567-5688, E-ISSN 1878-5050, Vol. 12, no 1, p. 14-14Article in journal (Other academic)
    Abstract [en]

    The protein composition of lipoproteins may serve as biomarkers or reveal underlying mechanisms during different states of disease. Here we have analysed the protein composition of LDL and HDL from patients with acute coronary syndrome (ACS) and patients receiving statins after previous ACS. Plasma samples were obtained from males, namely 12 healthy donors, 9 patients with ACS and 7 stable patients receiving statin treatment after previous ACS. LDL and HDL were isolated by two-step density ultracentrifugation. LDL proteins were analysed with two-dimensional gel electrophoresis and mass spectrometry. Paraoxonase 1 (PON-1) in HDL was analyzed with  SDSPAGE/Western Blot.

    Concentrations of apo A-IV, a1-antitrypsin and transthyretin were significantly increased (P < 0.05) in LDL from patients with ACS compared to healthy controls. In patients receiving statins, a1-antitrypsin remained increased while serum amyloid A4 was decreased. By western blot analysis, a non-significant increase in PON-1 was found in HDL from patients with ACS. Interestingly, a truncated form of PON-1 was detected in all patients with ACS but not in any of the controls.

    In conclusion, we confirm previous findings that LDL-associated transthyretin is a possible biomarker of myocardial infarction. Moreover, the increased concentration of the inflammatory marker a1-antitrypsin in LDL from both ACS patients and stable patients after ACS indicate that the enrichment does not only reflect an acute phase response. The presence of a truncated form of the antioxidant protein PON-1 in HDL may explain previous findings showing increased amounts but lower activity of PON-1 in patients with ACS.

  • 26.
    Ljunggren, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Levels, Johannes H M
    Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
    Turkina, Maria V
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Sundberg, Sofie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Bochem, Andrea E
    Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
    Hovingh, Kees
    Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
    Holleboom, Adriaan G
    Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Kuivenhoven, Jan Albert
    University of Groningen, Groningen, The Netherlands.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C2014In: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 8, no 3-4, p. 241-250Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Mutations in apolipoprotein A-I (apoA-I) may affect plasma high-density lipoprotein (HDL) cholesterol levels and the risk for cardiovascular disease but little is known about the presence and effects of circulating apoA-I variants. This study investigates whether the apoA-I mutations, apoA-I(L202P) and apoA-I(K131del) , are present on plasma HDL particles derived from heterozygote carriers and whether this is associated to changes in HDL protein composition.

    EXPERIMENTAL DESIGN: Plasma HDL of heterozygotes for either apoA-I(L202P) or apoA-I(K131del) and family controls was isolated using ultracentrifugation. HDL proteins were separated by 2DE and analyzed by MS.

    RESULTS: ApoA-I peptides containing apoA-I(L202P) or apoA-I(K131del) were identified in HDL from heterozygotes. The apoA-I(L202P) mutant peptide was less abundant than wild-type peptide while the apoA-I(K131del) mutant peptide was more abundant than wild-type peptide in the heterozygotes. Two-dimensional gel electrophoresis analyses indicated that, compared to controls, HDL in apoA-I(L202P) carriers contained less apoE and more zinc-α-2-glycoprotein while HDL from the apoA-I(K131del) heterozygotes contained more alpha-1-antitrypsin and transthyretin.

    CONCLUSIONS AND CLINICAL RELEVANCE: Both apoA-I(L202P) and apoA-I(K131del) were identified in HDL. In heterozygotes, these mutations have markedly differential effects on the concentration of wild-type apoA-I in the circulation, as well as the HDL proteome, both of which might affect the clinical phenotype encountered in the heterozygous carriers.

  • 27.
    Nosratabadi, Ali Reza
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Graff, Pål
    National Institute of Occupational Health, Oslo, Norway.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Ljungman, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Use of TEOM monitors for continuous long-term sampling of ambient particles for analysis of constituents and biological effects2019In: Air quality, atmosphere and health, ISSN 1873-9318, E-ISSN 1873-9326, Vol. 12, no 2, p. 161-171Article in journal (Refereed)
    Abstract [en]

    Many countries have implemented exposure limits for the concentration of ambient particular matter and do therefore have to monitor their concentration. This could be performed with TEOM monitors (Tapered Element Oscillating Microbalance-monitors) that contain a filter on which particles are collected. These filters are regularly exchanged for new ones. The aim of this study was to test the feasibility of collecting used filters from monitors at different locations and establishing a method to extract particles and then study them with respect to their ability to generate oxidants, their endotoxin content, and ability to activate inflammatory cells. Filters from nine geographically spread locations in Sweden were collected during a 21-month period by local technicians who then sent them to the laboratory where they were extracted and analyzed. The procedure to let local technicians perform the filter exchange and send used TEOM filters to the laboratory worked well. A method was established in which pyrogen-free water was used to extract particles that then were aliquoted and stored for later analysis. Particulate matter (PM10) from different locations showed both a considerable seasonal and spatial-dependent difference with respect to oxidative potential (oxidize glutathione), endotoxin content, and ability to activate blood monocytes to release interleukin-1β. This study shows that, instead of discarding TEOM filters, they can be collected and extracted so that particles that have been sampled in a standardized way could be analyzed with respect to variables that reflect their toxicity. This could be done at a low cost. In combination with information about the ambient particle concentration, such information could be helpful in the evaluation of differences in the risk of breathing air at various locations.

  • 28.
    Pettersson, C
    et al.
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Karlsson, H
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre. Östergötlands Läns Landsting.
    Fagerberg, B
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Stahlman, M
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Larsson, T
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Boren, J
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Wiklund, O
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Fogelstrand, L
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    LDL-ASSOCIATED LYSOZYME AND apoJ-SPECIFIC DISTRIBUTION IN INDIVIDUALS WITH TYPE 2 DIABETES AND THE METABOLIC SYNDROME in ATHEROSCLEROSIS SUPPLEMENTS, vol 11, issue 2, pp 114-1142010In: ATHEROSCLEROSIS SUPPLEMENTS, Elsevier Science B.V., Amsterdam. , 2010, Vol. 11, no 2, p. 114-114Conference paper (Refereed)
    Abstract [en]

    n/a

  • 29.
    Pettersson, Camilla
    et al.
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Ståhlman, Marcus
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Larsson, Thomas
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Fagerberg, Björn
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Wiklund, Olov
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Borén, Jan
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Fogelstrand, Linda
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    LDL-associated apolipoprotein J and lysozyme are associated with atherogenic properties of LDL found in type 2 diabetes and the metabolic syndrome2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 3, p. 306-321Article in journal (Refereed)
    Abstract [en]

    Objectives  Exchangeable low-density lipoprotein (LDL)-associated proteins can affect the atherogenic properties of LDL. Our aim was to analyze the protein composition of LDL from individuals with or without type 2 diabetes and the metabolic syndrome (T2DM) in relation to other LDL-particle characteristics, to assess whether certain proteins associate more with certain subclasses of LDL typical for T2DM, such as small, apoCIII-rich LDL. Design  LDL from two cohorts of 61-year-old men (n = 19 and 64) with or without T2DM was isolated using size-exclusion chromatography or deuterium oxide-based ultracentrifugation. LDL-associated proteins were identified using mass spectrometry and quantified using two-dimensional gel electrophoresis or enzyme-linked immunosorbent assay. Differently expressed LDL-associated proteins apolipoprotein (apo)J and lysozyme were also measured in serum from a third cohort of women (n = 71) with or without T2DM. Lysozyme binding to advanced glycation end product (AGE)-LDL was examined in vitro. Results  ApoJ and lysozyme were increased in LDL particles with increased apoCIII content and decreased cholesterol content. When isolated with SEC, LDL from individuals with T2DM contained more apoJ and lysozyme and less apoA1 than LDL from control individuals. LDL content of apoJ correlated with a smaller LDL-particle size. Serum levels of lysozyme, but not apoJ, were increased in individuals with T2DM. In vitro, lysozyme associated more with AGE-LDL than with unmodified LDL. Conclusions  Our results indicate that apoJ and lysozyme are increased in LDL with characteristics of small dense LDL in T2DM. Small dense LDL is easily glycated, and the increased affinity of lysozyme for AGE-LDL provides a possible partial explanation for an increase of lysozyme from those with type 2 diabetes.

  • 30.
    Ronn, M
    et al.
    Uppsala University.
    Ortiz-Nieto, F
    Uppsala University.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Kullberg, J
    Uppsala University.
    A rodent model for visceral obesity development evaluated by MRI in TOXICOLOGY LETTERS, vol 205, issue , pp S207-S2072011In: TOXICOLOGY LETTERS, Elsevier , 2011, Vol. 205, p. S207-S207Conference paper (Refereed)
    Abstract [en]

    n/a

  • 31.
    Rönn, Monika
    et al.
    Uppsala University, Sweden.
    Kullberg, Joel
    Uppsala University, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Berglund, Johan
    Uppsala University, Sweden.
    Malmberg, Filio
    Uppsala University, Sweden.
    Örberg, Jan
    Uppsala University, Sweden.
    Lind, Lars
    Uppsala University, Sweden.
    Ahlström, Håkan
    Uppsala University, Sweden.
    Lind, Monica P
    Uppsala University, Sweden.
    Bisphenol A exposure increases liver fat in juvenile fructose-fed Fischer 344 rats2013In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 303, p. 125-132Article in journal (Refereed)
    Abstract [en]

    Background

    Prenatal exposure to bisphenol A (BPA) has been shown to induce obesity in rodents. To evaluate if exposure also later in life could induce obesity or liver damage we investigated these hypothesises in an experimental rat model.

    Methods

    From five to fifteen weeks of age, female Fischer 344 rats were exposed to BPA via drinking water (0.025, 0.25 or 2.5 mg BPA/L) containing 5% fructose. Two control groups were given either water or 5% fructose solution. Individual weight of the rats was determined once a week. At termination magnetic resonance imaging was used to assess adipose tissue amount and distribution, and liver fat content. After sacrifice the left perirenal fat pad and the liver were dissected and weighed. Apolipoprotein A-I in plasma was analyzed by western blot.

    Results

    No significant effects on body weight or the weight of the dissected fad pad were seen in rats exposed to BPA, and MRI showed no differences in total or visceral adipose tissue volumes between the groups. However, MRI showed that liver fat content was significantly higher in BPA-exposed rats than in fructose controls (p = 0.04). BPA exposure also increased the apolipoprotein A-I levels in plasma (p < 0.0001).

    Conclusion

    We found no evidence that BPA exposure affects fat mass in juvenile fructose-fed rats. However, the finding that BPA in combination with fructose induced fat infiltration in the liver at dosages close to the current tolerable daily intake (TDI) might be of concern given the widespread use of this compound in our environment.

  • 32.
    Rönn, Monika
    et al.
    Uppsala University, Sweden.
    Lind, Monica
    Uppsala University, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Cvek, Katarina
    The Swedish university of Agricultural Science, Uppsala, Sweden.
    Berglund, Johan
    Uppsala University, Sweden.
    Malmberg, Filip
    Uppsala University, Sweden.
    Örberg, Jan
    Uppsala University, Sweden.
    Lind, Lars
    Uppsala University, Sweden.
    Kullberg, Joel
    Uppsala University, Sweden.
    Quantification of total and visceral adipose tissue in fructose-fed rats using water-fat separated single Echo MRI2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 9, p. E388-E395Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to setup a rodent model for modest weight gain and an MRI-based quantification of body composition on a clinical 1.5 T MRI system for studies of obesity and environmental factors and their possible association. Design and Methods: Twenty-four 4-week-old female Fischer rats were divided into two groups: one exposed group (n=12) and one control group (n 12). The exposed group was given drinking water containing fructose (5% for 7 weeks, then 20% for 3 weeks). The control group was given tap water. Before sacrifice, whole body MRI was performed to determine volumes of total and visceral adipose tissue and lean tissue. MRI was performed using a clinical 1.5 T system and a chemical shift based technique for separation of water and fat signal from a rapid single echo acquisition. Fat signal fraction was used to separate adipose and lean tissue. Visceral adipose tissue volume was quantified using semiautomated segmentation. After sacrifice, a perirenal fat pad and the liver were dissected and weighed. Plasma proteins were analyzed by Western blot. Results: The weight gain was 5.2% greater in rats exposed to fructose than in controls (P=0.042). Total and visceral adipose tissue volumes were 5.2 cm(3) (P=0.017) and 3.1 cm(3) (P=0.019) greater, respectively, while lean tissue volumes did not differ. The level of triglycerides and apolipoprotein A-I was higher (P=0.034, P=0.005, respectively) in fructose-exposed rats. Conclusions: The setup induced and assessed a modest visceral obesity and hypertriglyceridemia, making it suitable for further studies of a possible association between environmental factors and obesity.

  • 33.
    Sulaiman, Wan N Wan
    et al.
    University of Glasgow, U.K..
    Caslake, Muriel J
    University of Glasgow, U.K..
    Delles, Christian
    University of Glasgow, U.K..
    Karlsson, Helen
    Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Mulder, Monique T
    University of Glasgow, U.K, Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands.
    Graham, Delyth
    University of Glasgow, Glasgow, U.K..
    Freeman, Dilys J
    University of Glasgow, Glasgow, U.K..
    Does high-density lipoprotein protect vascular function in healthy pregnancy?2016In: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 130, no 7, p. 491-497Article in journal (Refereed)
    Abstract [en]

    The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals, these processes are usually associated with poor vascular function. However, maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma HDL (high-density lipoprotein), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vasodilatory, antioxidant, anti-thrombotic and anti-inflammatory effects, and can protect against endothelial cell damage. In pregnancy, the plasma HDL concentration starts to rise at 10 weeks of gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released, generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesized around the time of the establishment of the feto-placental circulation. In obese pregnancy and, to a greater extent, in pre-eclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesize that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in pre-eclampsia this fails to occur.

  • 34.
    Tian, Fei
    et al.
    Sahlgrenska Centre Cardiovasc & Metab Research.
    Zhou, Xianghua
    Sahlgrenska Centre Cardiovasc & Metab Research.
    Wikstrom, Johannes
    AstraZeneca Research & Development.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre. Östergötlands Läns Landsting, Centre for Medicine.
    Sjoland, Helen
    University of Gothenburg.
    Gan, Li-Ming
    University of Gothenburg.
    Boren, Jan
    Sahlgrenska Centre Cardiovasc & Metab Research.
    M Akyurek, Levent
    Sahlgrenska Centre Cardiovasc & Metab Research.
    Protein disulfide isomerase increases in myocardial endothelial cells in mice exposed to chronic hypoxia: a stimulatory role in angiogenesis2009In: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, ISSN 0363-6135, Vol. 297, no 3, p. H1078-H1086Article in journal (Refereed)
    Abstract [en]

    Previous studies have shown that exposure to chronic hypoxia protects against myocardial infarction, but little is known about the cellular and molecular mechanisms involved. Here we observed that chronic hypoxia for 3 wk resulted in improved survival of mice (from 64% to 83%), reduced infarction size (from 45 +/- 4% to 32 +/- 4%, P andlt; 0.05), increased cardiac ejection fraction (from 19 +/- 4% to 35 +/- 5%, P andlt; 0.05), coronary flow velocity under adenosine-induced hyperemia (from 58 +/- 2 to 75 +/- 5 cm/s, P andlt; 0.05), myocardial capillary density (from 3,772 +/- 162 to 4,760 +/- 197 capillaries/mm(2), P andlt; 0.01), and arteriolar density (from 8.04 +/- 0.76 to 10.34 +/- 0.69 arterioles/mm(2), P andlt; 0.05) 3 wk after myocardial infarction. With two-dimensional gel electrophoresis, we identified that protein disulfide isomerase (PDI) was highly upregulated in hypoxic myocardial capillary endothelial cells. The loss of PDI function in endothelial cells by small interfering RNA significantly increased the number of apoptotic cells (by 3.4-fold at hypoxia, P andlt; 0.01) and reduced migration (by 52% at hypoxia, P andlt; 0.001) and adhesion to collagen I (by 42% at hypoxia, P andlt; 0.01). In addition, the specific inhibition of PDI by PDI small interfering RNA (by 46%, P andlt; 0.01) and bacitracin (by 72%, P andlt; 0.001) reduced the formation of tubular structures by endothelial cells. Our data indicate that chronic hypoxic exposure improves coronary blood flow and protects the myocardium against infarction. These beneficial effects may be partly explained by the increased endothelial expression of PDI, which protects cells against apoptosis and increases cellular migration, adhesion, and tubular formation. The increased PDI expression in endothelial cells may be a novel mechanism to protect the myocardium against myocardial ischemic diseases.

  • 35.
    Örtegren Kugelberg, Unn
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Yin, Lan
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Öst, Anita
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes: segregation of specific proteins and functions2006In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 273, no 14, p. 3381-3392Article in journal (Refereed)
    Abstract [en]

    Caveolae are nearly ubiquitous plasma membrane domains that in adipocytes vary in size between 25 and 150 nm. They constitute sites of entry into the cell as well as platforms for cell signalling. We have previously reported that plasma membrane-associated caveolae that lack cell surface access can be identified by electron microscopy. We now report the identification, after density gradient ultracentrifugation, of a subclass of very high-density apparently closed caveolae that were not labelled by cell surface protein labelling of intact cells. These caveolae contained caveolin-1 and caveolin-2. Another class of high-density caveolae contained caveolin-1, caveolin-2 and specifically fatty acid transport protein-1, fatty acid transport protein-4, fatty acyl-CoA synthetase, hormone-sensitive lipase, perilipin, and insulin-regulated glucose transporter-4. This class of caveolae was specialized in fatty acid uptake and conversion to triacylglycerol. A third class of low-density caveolae contained the insulin receptor, class B scavenger receptor-1, and insulin-regulated glucose transporter-4. Small amounts of these proteins were also detected in the high-density caveolae. In response to insulin, the insulin receptor autophosphorylation and the amount of insulin-regulated glucose transporter-4 increased in these caveolae. The molar ratio of cholesterol to phospholipid in the three caveolae classes varied considerably, from 0.4 in very high-density caveolae to 0.9 in low-density caveolae. There was no correlation between the caveolar contents of caveolin and cholesterol. The low-density caveolae, with the highest cholesterol concentration, were particularly enriched with the cholesterol-rich lipoprotein receptor class B scavenger receptor-1, which mediated cholesteryl ester uptake from high-density lipoprotein and generation of free cholesterol in these caveolae, suggesting a specific role in cholesterol uptake/metabolism. These findings demonstrate a segregation of functions in caveolae subclasses.

1 - 35 of 35
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf