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Lindahl, Mats
Publications (10 of 39) Show all publications
Liang, W., Ward, L., Karlsson, H., Ljunggren, S., Li, W., Lindahl, M. & Yuan, X. (2016). Distinctive proteomic profiles among different regions of human carotid plaques in men and women. Scientific Reports, 6(26231)
Open this publication in new window or tab >>Distinctive proteomic profiles among different regions of human carotid plaques in men and women
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 26231Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2016
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-129495 (URN)10.1038/srep26231 (DOI)000376554600001 ()27198765 (PubMedID)
Note

Funding Agencies|Swedish Heart Lung Foundation; Linkoping University Hospital Research foundation; Swedish Institute; China Scholarship Council

Available from: 2016-06-20 Created: 2016-06-20 Last updated: 2019-04-17
Wåhlén, K., Fornander, L., Olausson, P., Ydreborg, K., Flodin, U., Graff, P., . . . Ghafouri, B. (2016). Protein profiles of nasal lavage fluid from individuals with work-related upper airway symptoms associated to moldy and damp buildings. Indoor Air, 26(5), 743-754
Open this publication in new window or tab >>Protein profiles of nasal lavage fluid from individuals with work-related upper airway symptoms associated to moldy and damp buildings
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2016 (English)In: Indoor Air, ISSN 0905-6947, E-ISSN 1600-0668, Vol. 26, no 5, p. 743-754Article in journal (Refereed) Published
Abstract [en]

Upper airway irritation is common among individuals working in moldy and damp buildings. The aim was to investigate effects on the protein composition of the nasal lining fluid. The prevalence of symptoms in relation to work was examined in 37 individuals working in two damp buildings. Microbial growth was confirmed in one of the buildings. Nasal lavage fluid was collected from 29 exposed subjects and 13 controls. Protein profiles were investigated with a proteomic approach and evaluated by multivariate statistical models. Subjects from both workplaces reported upper airway and ocular symptoms. Based on protein profiles, symptomatic subjects in the two workplaces were discriminated from each other and separated from healthy controls. The groups differed in proteins involved in inflammation and host defense. Measurements of innate immunity proteins showed a significant increa e of protein S100-A8 and decrease of SPLUNC1 in subjects from one workplace while alpha-1-antitrypsin was elevated in subjects from the other workplace, compared to healthy controls. The results show that protein profiles in nasal lavage fluid can be used to monitor airway mucosal effects in personnel working in damp buildings and indicate that the profile may be separate when the dampness is associated with the presence of molds.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
Sick building syndrome, proteomics, nasal mucosa, SPLUNC1, alpha-1-antitrypsin, protein S100-A8
National Category
Occupational Health and Environmental Health Infectious Medicine
Identifiers
urn:nbn:se:liu:diva-117339 (URN)10.1111/ina.12257 (DOI)000387348500009 ()
Note

Funding agencies: Research Council of South East Sweden [FORSS-222751, FORSS-389061]; Cancer and Allergy Foundation [150441]

Available from: 2015-04-23 Created: 2015-04-23 Last updated: 2018-01-11Bibliographically approved
Ljunggren, S. A., Levels, J. H., Hovingh, K., Holleboom, A. G., Vergeer, M., Argyri, L., . . . Karlsson, H. (2015). Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1.. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1851(12), 1587-1595
Open this publication in new window or tab >>Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1.
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2015 (English)In: 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) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
ApoE; ApoL-1; HDL; LDL/VLDL; P297S; SR-B1
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-122723 (URN)10.1016/j.bbalip.2015.09.006 (DOI)000364252800008 ()26454245 (PubMedID)
Note

Funding agencies: EUs Sixth Framework Program [037631]; European Union [FP7-603091-2]; CardioVascular Research Initiative [CVON2011-16]; Research Council of South East Sweden [FORSS-3755]; County Council of Ostergotland (C-ALF); Faculty of Health Sciences in Linkoping; Ven

Available from: 2015-11-18 Created: 2015-11-18 Last updated: 2018-05-27
Kontush, A., Lindahl, M., Lhomme, M., Calabresi, L., Chapman, M. J. & Davidson, W. S. (2015). Structure of HDL: particle subclasses and molecular components. In: High Density Lipoproteins – from biological understanding to clinical exploitation: (pp. 3-51). Springer, 224
Open this publication in new window or tab >>Structure of HDL: particle subclasses and molecular components
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2015 (English)In: High Density Lipoproteins – from biological understanding to clinical exploitation, Springer, 2015, Vol. 224, p. 3-51Chapter in book (Refereed)
Abstract [en]

A molecular understanding of high-density lipoprotein (HDL) will allow a more complete grasp of its interactions with key plasma remodelling factors and with cell-surface proteins that mediate HDL assembly and clearance. However, these particles are notoriously heterogeneous in terms of almost every physical, chemical and biological property. Furthermore, HDL particles have not lent themselves to high-resolution structural study through mainstream techniques like nuclear magnetic resonance and X-ray crystallography; investigators have therefore had to use a series of lower resolution methods to derive a general structural understanding of these enigmatic particles. This chapter reviews current knowledge of the composition, structure and heterogeneity of human plasma HDL. The multifaceted composition of the HDL proteome, the multiple major protein isoforms involving translational and posttranslational modifications, the rapidly expanding knowledge of the HDL lipidome, the highly complex world of HDL subclasses and putative models of HDL particle structure are extensively discussed. A brief history of structural studies of both plasma-derived and recombinant forms of HDL is presented with a focus on detailed structural models that have been derived from a range of techniques spanning mass spectrometry to molecular dynamics.

Place, publisher, year, edition, pages
Springer, 2015
Series
Handbook of Experimental Pharmacology, ISSN 0171-2004, E-ISSN 1865-0325 ; 244
National Category
Structural Biology
Identifiers
urn:nbn:se:liu:diva-126602 (URN)10.1007/978-3-319-09665-0_1 (DOI)25522985 (PubMedID)978-3-319-09664-3 (ISBN)978-3-319-09665-0 (ISBN)
Available from: 2016-03-31 Created: 2016-03-31 Last updated: 2018-12-11Bibliographically approved
Ljunggren, S., Levels, J. H., Turkina, M. V., Sundberg, S., Bochem, A. E., Hovingh, K., . . . Karlsson, H. (2014). ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C. PROTEOMICS - Clinical Applications, 8(3-4), 241-250
Open this publication in new window or tab >>ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C
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2014 (English)In: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 8, no 3-4, p. 241-250Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
National Category
Cell and Molecular Biology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-105992 (URN)10.1002/prca.201300014 (DOI)000334251600013 ()24273187 (PubMedID)
Available from: 2014-04-16 Created: 2014-04-16 Last updated: 2018-01-11
Ljunggren, S. A., Helmfrid, I., Salihovic, S., van Bavel, B., Wingren, G., Lindahl, M. & Karlsson, H. (2014). Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer.. Environment International, 65, 93-9
Open this publication in new window or tab >>Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer.
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2014 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 65, p. 93-9Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2014
National Category
Clinical Medicine Other Basic Medicine
Identifiers
urn:nbn:se:liu:diva-104755 (URN)10.1016/j.envint.2013.12.017 (DOI)000334728500010 ()24472825 (PubMedID)
Available from: 2014-02-25 Created: 2014-02-25 Last updated: 2018-01-11
Fornander, L., Ghafouri, B., Lindahl, M. & Graff, P. (2013). Airway irritation among indoor swimming pool personnel: trichloramine exposure, exhaled NO and protein profiling of nasal lavage fluids. International Archives of Occupational and Environmental Health, 86(5), 571-580
Open this publication in new window or tab >>Airway irritation among indoor swimming pool personnel: trichloramine exposure, exhaled NO and protein profiling of nasal lavage fluids
2013 (English)In: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 86, no 5, p. 571-580Article in journal (Refereed) Published
Abstract [en]

Purpose

Occurrence of airway irritation among indoor swimming pool personnel was investigated. The aims of this study were to assess trichloramine exposure levels and exhaled nitric oxide in relation to the prevalence of airway symptoms in swimming pool facilities and to determine protein effects in the upper respiratory tract.

Methods

The presence of airway symptoms related to work was examined in 146 individuals working at 46 indoor swimming pool facilities. Levels of trichloramine, as well as exhaled nitric oxide, were measured in five facilities with high prevalence of airway irritation and four facilities with no airway irritation among the personnel. Nasal lavage fluid was collected, and protein profiles were determined by a proteomic approach.

Results

17 % of the swimming pool personnel reported airway symptoms related to work. The levels of trichloramine in the swimming pool facilities ranged from 0.04 to 0.36 mg/m3. There was no covariance between trichloramine levels, exhaled nitric oxide and prevalence of airway symptoms. Protein profiling of the nasal lavage fluid showed that the levels alpha-1-antitrypsin and lactoferrin were significantly higher, and S100-A8 was significantly lower in swimming pool personnel.

Conclusions

This study confirms the occurrence of airway irritation among indoor swimming pool personnel. Our results indicate altered levels of innate immunity proteins in the upper airways that may pose as potential biomarkers. However, swimming pool facilities with high prevalence of airway irritation could not be explained by higher trichloramine exposure levels. Further studies are needed to clarify the environmental factors in indoor swimming pools that cause airway problems and affect the immune system.

Place, publisher, year, edition, pages
Springer, 2013
Keywords
Innate immunity, Occupational medicine, roteomics, Upper respiratory tract
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-86713 (URN)10.1007/s00420-012-0790-4 (DOI)000320394300008 ()22729567 (PubMedID)
Available from: 2012-12-25 Created: 2012-12-25 Last updated: 2017-12-06Bibliographically approved
Fornander, L., Graff, P., Wåhlén, K., Ydreborg, K., Flodin, U., Leanderson, P., . . . Ghafouri, B. (2013). Airway symptoms and biological markers in nasal lavage fluid in subjects exposed to metalworking fluids. PLoS ONE, 8(12), e83089
Open this publication in new window or tab >>Airway symptoms and biological markers in nasal lavage fluid in subjects exposed to metalworking fluids
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, p. e83089-Article in journal (Refereed) Published
Abstract [en]

BACKGROUNDS: Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in nasal mucous membranes, and evaluate preventive actions.

METHODS: The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach.

RESULTS: Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and β2-microglobulin among workers with airway symptoms.

CONCLUSIONS: This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted.

Place, publisher, year, edition, pages
Public Library of Science, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103739 (URN)10.1371/journal.pone.0083089 (DOI)000329325200035 ()24391738 (PubMedID)
Available from: 2014-01-24 Created: 2014-01-24 Last updated: 2019-02-11Bibliographically approved
Karlsson, H., Ljunggren, S., Ahrén, M., Ghafouri, B., Uvdal, K., Lindahl, M. & Ljungman, A. (2012). Two-dimensional gel electrophoresis and mass spectrometry in studies of nanoparticle-protein interactions. In: Sameh Magdeldin (Ed.), Gel electrophoresis-Advanced Techniques: (pp. 1-32). Rijeka, Croatia: In Tech
Open this publication in new window or tab >>Two-dimensional gel electrophoresis and mass spectrometry in studies of nanoparticle-protein interactions
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2012 (English)In: 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.

Place, publisher, year, edition, pages
Rijeka, Croatia: In Tech, 2012
Keywords
Proteins, Nanoparticles, Gelelectrophoresis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-78397 (URN)10.5772/38085 (DOI)978-953-51-0457-5 (ISBN)
Available from: 2012-06-11 Created: 2012-06-11 Last updated: 2015-05-29Bibliographically approved
Ljunggren, S., Karlsson, H., Mortstedt, H., Hellstrom, L., Perk, J., Besler, C., . . . Lindahl, M. (2011). CHANGES IN HUMAN LIPOPROTEIN COMPOSITION IN PATIENTS WITH ACUTE CORONARY SYNDROME in ATHEROSCLEROSIS SUPPLEMENTS, vol 12, issue 1, pp 14-14. In: ATHEROSCLEROSIS SUPPLEMENTS. Paper presented at 79th EAS Congress (pp. 14-14). Elsevier Science B.V., Amsterdam., 12(1)
Open this publication in new window or tab >>CHANGES IN HUMAN LIPOPROTEIN COMPOSITION IN PATIENTS WITH ACUTE CORONARY SYNDROME in ATHEROSCLEROSIS SUPPLEMENTS, vol 12, issue 1, pp 14-14
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2011 (English)In: ATHEROSCLEROSIS SUPPLEMENTS, Elsevier Science B.V., Amsterdam. , 2011, Vol. 12, no 1, p. 14-14Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-75746 (URN)10.1016/S1567-5688(11)70059-9 (DOI)000300159000059 ()
Conference
79th EAS Congress
Available from: 2012-03-09 Created: 2012-03-09 Last updated: 2012-03-09
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