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  • 1.
    Alfredsson, Joakim
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Käll, Anna
    Tilander, Hanna
    Janzon, Magnus
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Swahn, Eva
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Jonasson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Sex matters-lipid goal achievement in a population admitted to a coronary care unit2008Inngår i: X Svenska Kardiovaskulära Vårmötet,2008, 2008Konferansepaper (Fagfellevurdert)
    Abstract [en]

     Number A13731

  • 2.
    Alfredsson, Joakim
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Lindahl, Tomas L
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Gustafsson, Kerstin M
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Janzon, Magnus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Logander, Elisabeth
    Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Swahn, Eva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel: Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).2015Inngår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, nr 2, s. 335-340Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.

    METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.

    CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.

  • 3.
    Backteman, Karin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Andersson, Carina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Lymphocyte Subpopulations in Lymph Nodes and Peripheral Blood: A Comparison between Patients with Stable Angina and Acute Coronary Syndrome2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 3Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Atherosclerosis is characterized by a chronic inflammatory response involving activated T cells and impairment of natural killer (NK) cells. An increased T cell activity has been associated with plaque instability and risk of acute cardiac events. Lymphocyte analyses in blood are widely used to evaluate the immune status. However, peripheral blood contains only a minor proportion of lymphocytes. In this study, we hypothesized that thoracic lymph nodes from patients with stable angina (SA) and acute coronary syndrome (ACS) might add information to peripheral blood analyses. less thanbrgreater than less thanbrgreater thanMethods: Peripheral blood and lymph nodes were collected during coronary by-pass surgery in 13 patients with SA and 13 patients with ACS. Lymphocyte subpopulations were assessed by flow cytometry using antibodies against CD3, CD4, CD8, CD19, CD16/56, CD25, Foxp3, CD69, HLA-DR, IL-18 receptor (R) and CCR4. less thanbrgreater than less thanbrgreater thanResults: Lymph nodes revealed a lymphocyte subpopulation profile substantially differing from that in blood including a higher proportion of B cells, lower proportions of CD8(+) T cells and NK cells and a 2-fold higher CD4/CD8 ratio. CD4(+)CD69(+) cells as well as Foxp3(+) regulatory T cells were markedly enriched in lymph nodes (p andlt; 0.001) while T helper 1-like (CD4(+)IL-18R(+)) cells were more frequent in blood (p andlt; 0.001). The only significant differences between ACS and SA patients involved NK cells that were reduced in the ACS group. However, despite being reduced, the NK cell fraction in ACS patients contained a significantly higher proportion of IL-18R(+) cells compared with SA patients (p andlt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: There were several differences in lymphocyte subpopulations between blood and lymph nodes. However, the lymphocyte perturbations in peripheral blood of ACS patients compared with SA patients were not mirrored in lymph nodes. The findings indicate that lymph node analyses in multivessel coronary artery disease may not reveal any major changes in the immune response that are not detectable in blood.

  • 4.
    Backteman, Karin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Cytomegalovirus seropositivity is a major determinant of CD28null T cell expansion in patients with coronary artery disease2014Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Objective: Accumulation of CD4+28null cells, with a proinflammatory and senescent phenotype, has been associated with unstable conditions of coronary artery disease (CAD). Human cytomegalovirus (HCMV) is known to exert profound effects on T cells, including loss of CD28. Here, we longitudinally assessed the proportions of CD28null and CD28nullCD57+ cells in CD4+ and CD8+ T cell populations of patients with CAD and related the findings to HCMV seropositivity.

    Methods: HCMV antibody levels and expression of CD28 and CD57 on CD4+ and CD8+ T cells were analysed in 31 patients with acute coronary syndrome (ACS), 34 patients with stable angina (SA) and 37 healthy controls. Samples were taken prior to 34 coronary angiography and after 3 and 12 months. In a subsample, HCMV-specific IFN-γ and  TNF production was assessed ex vivo.

    Results: Increased proportions of CD4+CD28null, but not CD8+CD28null cells, were significantly associated with presence of CAD. Significant increases in CD28null 37 and CD28nullCD57+ cells occurred within CD4+ and CD8+ T cell compartments in both ACS and SA patients during 12-month follow-up. HCMV was the major determinant of CD28null and CD28nullCD57+ T cell levels in both patients and controls (p <0.001). There were no obvious signs of CMV reactivation in patients.

    Conclusion: HCMV was a major determinant of the presence of CD28null and CD28nullCD57+ T cells in patients with CAD, independent of clinical stage. Findings also indicate that HCMV might have a large impact on the T cell aging process that occurred in patients after a cardiac event.

  • 5.
    Backteman, Karin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    LYMPHOCYTE SUBPOPULATIONS IN LYMPH NODES AND PERIPHERAL BLOOD. A COMPARISON BETWEEN PATIENTS WITH STABLE ANGINA AND ACUTE CORONARY SYNDROME in INFLAMMATION RESEARCH, vol 60, issue , pp 215-2162011Inngår i: INFLAMMATION RESEARCH, Springer Science Business Media , 2011, Vol. 60, s. 215-216Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 6.
    Backteman, Karin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Natural killer (NK) cell deficit in coronary artery disease: no aberrations in phenotype but sustained reduction of NK cells is associated with low-grade inflammation2014Inngår i: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 175, nr 1, s. 104-112Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Although reduced natural killer (NK) cell levels have been reported consistently in patients with coronary artery disease (CAD), the clinical significance and persistence of this immune perturbation is not clarified. In this study we characterized the NK cell deficit further by determining (i) differentiation surface markers and cytokine profile of NK cell subsets and (ii) ability to reconstitute NK cell levels over time. Flow cytometry was used to analyse NK cell subsets and the intracellular cytokine profile in 31 patients with non-ST elevation myocardial infarction (non-STEMI), 34 patients with stable angina (SA) and 37 healthy controls. In blood collected prior to coronary angiography, the proportions of NK cells were reduced significantly in non-STEMI and SA patients compared with controls, whereas NK cell subset analyses or cytokine profile measurements did not reveal any differences across groups. During a 12-month follow-up, the proportions of NK cells increased, although not in all patients. Failure to reconstitute NK cell levels was associated with several components of metabolic syndrome. Moreover, interleukin (IL)-6 levels remained high in patients with sustained NK cell deficit, whereas a decline in IL-6 (P < 0·001) was seen in patients with a pronounced increase in NK cells. In conclusion, we found no evidence that reduction of NK cells in CAD patients was associated with aberrations in NK cell phenotype at any clinical stage of the disease. Conversely, failure to reconstitute NK cell levels was associated with a persistent low-grade inflammation, suggesting a protective role of NK cells in CAD.

  • 7.
    Bergström, Ida
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Backteman, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    ACCUMULATION OF CD56+CD8+T CELLS IN PATIENTS WITH CORONARY ARTERY DISEASE: HIGH PRODUCTION OF IFN-GAMMA BUT DIFFERENTIAL EXPRESSION OF ANNEXIN 1 in INFLAMMATION RESEARCH, vol 60, issue , pp 223-2232011Inngår i: INFLAMMATION RESEARCH, Springer Science Business Media , 2011, Vol. 60, s. 223-223Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 8.
    Bergström, Ida
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Backteman, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Lundberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Persistent accumulation of interferon-gamma-producing CD8(+)CD56(+) T cells in blood from patients with coronary artery disease2012Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, nr 2, s. 515-520Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: There is emerging evidence for CD8(+) T cell alterations in blood from patients with coronary artery disease (CAD). We examined whether the distribution and phenotype of CD8(+)CD56(+) T cells differed according to the clinical manifestation of CAD. less thanbrgreater than less thanbrgreater thanMethods: Patients with acute coronary syndrome (ACS, n = 30), stable angina (SA, n = 34) and controls (n = 36) were included. Blood was collected before and up to 12 months after referral for coronary investigation. CD8(+)CD56(+) T cells were assessed by flow cytometry for expression of surface markers, apoptosis, and intracellular expression of cytokines. less thanbrgreater than less thanbrgreater thanResults: The proportions of CD8(+)CD56(+) T cells were significantly higher in both ACS and SA patients compared with controls, and remained so after 3 and 12 months. This was independent of age, sex, systemic inflammation and cytomegalovirus seropositivity. CD8(+)CD56(+) T cells differed from CD8(+)CD56(-) T cells in terms of lower CD28 expression and fewer apoptotic cells. Both CD8(+) T cell subsets were positive for interferon (IFN)-gamma and tumor necrosis factor, although IFN-gamma was significantly more confined to the CD8(+)CD56(+) T cells. less thanbrgreater than less thanbrgreater thanConclusion: The persistent accumulation of CD8(+)CD56(+) T cells in ACS and SA patients share several features with immunological aging. It also contributes to a larger IFN-gamma(+) pool in blood, and may thereby hypothetically drive the atherosclerotic process in a less favorable direction.

  • 9.
    Bergström, Ida
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Lundberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Simon
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Särndahl, Eva
    Department of Clinical Medicine, School of Health and Medical Sciences, and iRiSC - Inflammatory 18 Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Annexin A1 expression in blood mononuclear cells: a potential marker of glucocorticoid activity in patients with coronary artery disease2014Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    An imbalance between pro- and anti-inflammatory actions is believed to drive progression of atherosclerosis. Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of anti-inflammatory effects of glucocorticoids. Here, we investigated whether expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) was altered in patients with coronary artery disease (CAD) and also related findings to glucocorticoid sensitivity ex vivo.

    We included 57 patients 6-12 months after acute coronary syndrome (ACS), 10 patients with ACS, and healthy controls. AnxA1 mRNA was measured in PBMCs and AnxA1 protein was assessed in monocytes and lymphocyte subsets by flow cytometry. In post-ACS patients and controls, glucocorticoid sensitivity was determined by measuring inhibitory effects of dexamethasone on LPS46 induced cytokine secretion.

    AnxA1 mRNA levels in PBMCs were higher in patients compared with controls, although most pronounced in ACS patients. AnxA1 protein was most abundant in the monocyte fraction. ACS patients exhibited the highest levels of cell surface-associated AnxA1 protein while levels in post-ACS patients and controls were similar. Ex vivo assays showed that PBMCs from post-ACS patients were more prone to release IL-6. Glucocorticoid sensitivity correlated with cell surface-associated AnxA1 protein in peripheral monocytes. Dexamethasone also induced upregulation of AnxA1 mRNA.

    AnxA1 expression in PBMCs is closely associated with glucocorticoid actions and cell surface associated AnxA1 appears to be a marker of glucocorticoid sensitivity. Although still speculative, a “normal” expression of cell surface-associated AnxA1 in post-ACS patients may suggest that glucocorticoid actions in vivo are insufficient to provide adequate anti-inflammatory effects in these patients.

  • 10.
    Bergström, Ida
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Lundberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Reutelingsperger, Chris
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Särndahl, Eva
    Department of Clinical Medicine, School of Health and Medical Sciences, and iRiSC - Inflammatory 18 Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Higher expression of annexin A1 in 1 CD56+ than in CD56-T cells: Potential implications for coronary artery disease2014Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background: Increased proportions of circulating proinflammatory CD56+ T cells have been reported in patients with coronary artery disease (CAD). Yet, little is known about regulation of these cells. In the present study, we investigated the expression and potential role of the glucocorticoid-mediated protein annexin A1 (AnxA1) in CD56+ and CD56-T cell subsets, with focus on CAD.

    Methods and Results: We included totally 52 healthy individuals, 28 patients with acute coronary syndrome (ACS) and 57 patients with a history of ACS. AnxA1 mRNA expression was assessed in peripheral blood mononuclear cells. AnxA1 protein expression (total and cell surface-associated) was measured by whole blood flow cytometry in circulating CD56+ and CD56- T cell subsets. Furthermore, inhibitory effects of dexamethasone and/or recombinant AnxA1 on cytokine secretion by CD56+ and CD56- T cells were explored in vitro. We found that CD56+ T cells (the majority CD8+), expressed higher levels of AnxA1 mRNA and protein than did CD56- T cells. When comparing CAD patients with healthy controls, significantly higher levels of cell surface-associated AnxA1 expression were seen in patients, most pronounced in ACS patients. In vitro, dexamethasone reduced cytokine secretion by CD56+ T cells, whereas AnxA1 alone had no effect, and AnxA1 combined with dexamethasone abolished the dexamethasone-induced suppressive effects.

    Conclusion: AnxA1 was expressed more abundantly in proinflammatory CD56+ T cells. Patients with ACS exhibited increased levels of cell surface-associated AnxA1, thus indicating increased activation of the AnxA1 pathway. Our data further suggested that AnxA1 might counteract glucocorticoid mediated anti-inflammatory effects in T cells.

  • 11.
    Bjarnegård, Niclas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Arnqvist, Hans J.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Lindström, Torbjörn
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, A.
    Department of Internal Medicin, Jönköping Hospital, Jönköping, Sweden.
    Länne, Toste
    Linköpings universitet, Institutionen för medicin och hälsa, Fysiologi. Linköpings universitet, Hälsouniversitetet.
    Impaired endothelial independent vasodilatation in women with type 1 diabetes2008Manuskript (preprint) (Annet vitenskapelig)
  • 12.
    Bjarnegård, Niclas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Arnqvist, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Lindström, Torbjörn
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Jonsson, Anders
    Jönköping Hospital.
    Länne, Toste
    Linköpings universitet, Institutionen för medicin och hälsa, Fysiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Long-term hyperglycaemia impairs vascular smooth muscle cell function in women with type 1 diabetes mellitus2009Inngår i: DIABETES and VASCULAR DISEASE RESEARCH, ISSN 1479-1641, Vol. 6, nr 1, s. 25-31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Observations of increased stiffness in the elastic aorta in women with diabetes, but not men, emphasise the need for further analysis regarding early abnormalities in arterial wall properties of women with type 1 diabetes mellitus (DM).

    Ultrasound was used to study the wall properties of the distal brachial artery (BA) in 37 type 1 diabetic women (aged 22-45 years) without evident complications and in 53 controls (C). Blood samples were drawn for later analysis.

    Flow-mediated dilatation (FMD) was slightly lower in DM than C, 8.1 +/- 4.3% vs. 10.3 +/- 4.9% (p&lt;0.05), and nitrate-mediated dilatation (NMD) was markedly lower, 21.7 +/- 6.6% vs. 31.4 +/- 5.7% (p&lt;0.001). Lumen diameter, intima-media thickness and distensibility were similar in DM and C. Insulin-like growth factor (IGF-1) was lower in DM than C, 231 +/- 65 vs. 349 +/- 68 ng/ml (p&lt;0.001). Glycosylated haemoglobin (HbA(1C)) and matrix metalloproteinase (MMP-9) were independent predictors of the reduced NMD in the DM.

    Brachial artery responsiveness to an exogenous donor of nitric oxide (NO) was markedly reduced in type 1 diabetic women despite only limited reduction in endothelium-dependent dilatation. The negative association between NMD and HbA(1C) suggests that long-term hyperglycaemia impairs vascular smooth muscle cell function in DM.

  • 13. Cherfan, P
    et al.
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Jonasson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Effects of simvastatin on human t-cells in vivo2005Inngår i: European Atherosclerosis Society Congress,2005, 2005Konferansepaper (Annet vitenskapelig)
  • 14. Cherfan, P
    et al.
    Tompa, A
    Wikby, A
    Löfgren, S
    Jonasson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Effects of simvastatin on human T cells in vivo2007Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 193, nr 1, s. 186-192Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The use of statins has shown several anti-inflammatory actions, including modulatory effects on T cells in vitro. Since the effects on human T cells in vivo are less clarified, our aim was to investigate the effects of simvastatin on human T cells in vivo and ex vivo. Methods and results: A randomized, double-blind, placebo-controlled study design was applied. Eighty volunteers with mild to moderate hypercholesterolemia received either simvastatin 40 mg or placebo for 6 weeks. The serum levels of C-reactive protein (CRP) were significantly reduced by simvastatin. The proportions of CD4+ and CD8+ T cell subsets expressing early (CD25) or late (HLA-DR) activation markers, as assessed by flow cytometry, were not changed by simvastatin. However, simvastatin tended to increase the density of HLA-DR and L-selectin per CD8+ T cell. The T helper(h)1/Th2 response was evaluated by stimulatory assays followed by intra-cellular staining of interferon-γ and interleukin-4. Simvastatin treatment did not affect the Th1 response but the results indicated a potential to suppress Th2. Conclusion: Simvastatin treatment resulted in a few discrete changes as regards peripheral T cells. However, the findings do not provide evidence that simvastatin-induced anti-inflammatory actions are related to any significant modulatory effects on human T cells in clinically healthy men with hypercholesterolemia. © 2006 Elsevier Ireland Ltd. All rights reserved.

  • 15.
    Eriksson, Andreas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Hedbäck, Bo
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Whiss, Per A.
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Monitoring platelet inhibiting treatment in coronary heart disease by static platelet adhesion2007Konferansepaper (Annet vitenskapelig)
  • 16.
    Eriksson, Andreas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Hedbäck, Bo
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Whiss, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Static platelet adhesion, flow cytometry and serum TXB2 levels for monitoring platelet inhibiting treatment with ASA and clopidogrel in coronary artery disease: a randomised cross-over study2009Inngår i: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 7, nr 42Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Despite the use of anti-platelet agents such as acetylsalicylic acid (ASA) and clopidogrel in coronary heart disease, some patients continue to suffer from atherothrombosis. This has stimulated development of platelet function assays to monitor treatment effects. However, it is still not recommended to change treatment based on results from platelet function assays. This study aimed to evaluate the capacity of a static platelet adhesion assay to detect platelet inhibiting effects of ASA and clopidogrel. The adhesion assay measures several aspects of platelet adhesion simultaneously, which increases the probability of finding conditions sensitive for anti-platelet treatment. Methods: With a randomised cross-over design we evaluated the anti-platelet effects of ASA combined with clopidogrel as well as monotherapy with either drug alone in 29 patients with a recent acute coronary syndrome. Also, 29 matched healthy controls were included to evaluate intra-individual variability over time. Platelet function was measured by flow cytometry, serum thromboxane B-2 (TXB2)-levels and by static platelet adhesion to different protein surfaces. The results were subjected to Principal Component Analysis followed by ANOVA, t-tests and linear regression analysis. Results: The majority of platelet adhesion measures were reproducible in controls over time denoting that the assay can monitor platelet activity. Adenosine 5-diphosphate (ADP)-induced platelet adhesion decreased significantly upon treatment with clopidogrel compared to ASA. Flow cytometric measurements showed the same pattern (r(2) = 0.49). In opposite, TXB2-levels decreased with ASA compared to clopidogrel. Serum TXB2 and ADP-induced platelet activation could both be regarded as direct measures of the pharmacodynamic effects of ASA and clopidogrel respectively. Indirect pharmacodynamic measures such as adhesion to albumin induced by various soluble activators as well as SFLLRN-induced activation measured by flow cytometry were lower for clopidogrel compared to ASA. Furthermore, adhesion to collagen was lower for ASA and clopidogrel combined compared with either drug alone. Conclusion: The indirect pharmacodynamic measures of the effects of ASA and clopidogrel might be used together with ADP-induced activation and serum TXB2 for evaluation of anti-platelet treatment. This should be further evaluated in future clinical studies where screening opportunities with the adhesion assay will be optimised towards increased sensitivity to anti-platelet treatment.

  • 17.
    Garvin, Peter
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Socialmedicin och folkhälsovetenskap. Linköpings universitet, Hälsouniversitetet.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Kristenson, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Socialmedicin och folkhälsovetenskap. Linköpings universitet, Hälsouniversitetet.
    Association between ambulatory saliva cortisol levels and plasma levels of matrix metalloproteinase-9 in a normal populationManuskript (Annet vitenskapelig)
    Abstract [en]

    Background: Psychosocial strain has been demonstrated to be a risk factor for coronary artery disease (CAD) and also to be associated with a dysfunctional HPA-axis. Based on a proposal on cortisol resistance in maladaptive monocytes as a potential mechanism linking psychosocial strain with CAD, this study aimed at testing the association between levels of salivary cortisol and matrix metalloproteinase-9 (MMP-9) in a normal population.

    Methods: 359 participants (50 % women) aged 45-69 were enrolled to this study, randomly drawn from a normal population in Sweden. Saliva samples were collected thrice per day (at awakening, 30 minutes after awakening, and just before going to bed) during three consecutive days. Cortisol levels at awakening and 30 minutes after awakening were used to estimate the diurnal peak. Cortisol was analyzed using a radioimmunoassay method. MMP-9 was measured in plasma using an ELISA-method.

    Results: After adjustment for age and sex, significant trends regarding MMP-9 were found both for cortisol peak quintiles (beta +1.9 ng/mL per quintile, p=0.029) and cortisol evening values (beta +2.1 ng/ml per quintile, p=0.017). These findings were consistent in regressions either excluding participants with known diagnoses of myocardial infarction, angina pectoris, rheumatoid arthritis, diabetes, cancer with ongoing treatment, chronic obstructive lung disease, osteoporosis and hypothyroidism, or adjusting for these diseases, also after adjustment for cardiovascular risk factors.

    Conclusions: The associations found between cortisol levels and MMP-9 in a normal population hint at a potential pathway linking prolonged psychosocial strain with cardiovascular events.

  • 18.
    Garvin, Peter
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Socialmedicin och folkhälsovetenskap.
    Jonasson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Carstensen, John
    Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutionen för hälsa och samhälle, Tema hälsa och samhälle.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Kristenson, Margareta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Socialmedicin och folkhälsovetenskap. Östergötlands Läns Landsting, Folkhälsovetenskapligt centrum, Folkhälsovetenskapligt centrum.
    Levels of circulating matrix metallo proteinase-9 is associated to psychosocial factors and lifestyle2006Inngår i: XIV International Symposium on Atherosclerosis,2006, 2006Konferansepaper (Annet vitenskapelig)
  • 19.
    Garvin, Peter
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Socialmedicin och folkhälsovetenskap.
    Jonasson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Kristenson, Margareta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och samhälle, Socialmedicin och folkhälsovetenskap. Östergötlands Läns Landsting, Folkhälsovetenskapligt centrum, Folkhälsovetenskapligt centrum.
    Nijm, Johnny
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi.
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Psychosocial factors in atherosclerosis2006Inngår i: XIV International Symposium on Atherosclerosis,2006, 2006Konferansepaper (Annet vitenskapelig)
  • 20.
    Garvin, Peter
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Falk, Magnus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Kristenson, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Plasma Matrix Metalloproteinase-9 Levels Predict First-Time Coronary Heart Disease: An 8-Year Follow-Up of a Community-Based Middle Aged Population2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 9, s. e0138290-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The enzyme in matrix metalloproteinase (MMP)-9 has been suggested to be an important determinant of plaque degradation. While several studies have shown elevated levels in patients with coronary heart disease, results in prospective population based studies evaluating MMP-9 in relation to first time coronary events have been inconclusive. As of today, there are four published studies which have measured MMP-9 in serum and none using plasma. Measures of MMP-9 in serum have been suggested to have more flaws than measures in plasma. Aim To investigate the independent association between plasma levels of MMP-9 and first-time incidence of coronary events in an 8-year follow-up. Material and Methods 428 men and 438 women, aged 45-69 years, free of previous coronary events and stroke at baseline, were followed-up. Adjustments were made for sex, age, socioeconomic position, behavioral and cardiovascular risk factors, chronic disease at baseline, depressive symptoms, interleukin-6 and C-reactive protein. Results 53 events were identified during a risk-time of 6 607 person years. Hazard ratio (HR) for MMP-9 after adjustment for all covariates were HR = 1.44 (1.03 to 2.02, p = 0.033). Overall, the effect of adjustments for other cardiovascular risk factors was low. Conclusion Levels of plasma MMP-9 are independently associated with risk of first-time CHD events, regardless of adjustments. These results are in contrast to previous prospective population-based studies based on MMP-9 in serum. It is essential that more studies look at MMP-9 levels in plasma to further evaluate the association with first coronary events.

  • 21.
    Garvin, Peter
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Socialmedicin och folkhälsovetenskap.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Filosofiska fakulteten.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Filosofiska fakulteten. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Kristenson, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Socialmedicin och folkhälsovetenskap. Linköpings universitet, Hälsouniversitetet.
    Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population2008Inngår i: PLoS ONE, ISSN 1932-6203, Vol. 3, nr 3, s. e1774-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Elevated levels of circulating matrix metalloproteinase-9 (MMP-9) have been demonstrated in patients with established coronary artery disease (CAD). The aim of this study was to analyse levels of MMP-9 in a population free from symptomatic CAD and investigate their associations with cardiovascular (CV) risk factors, including C-reactive protein (CRP).

     

    Methods: A cross-sectional study was performed in a population based random sample aged 45–69 (n = 345, 50% women). MMP-9 levels were measured in EDTA-plasma using an ELISA-method. CV risk factors were measured using questionnaires and standard laboratory methods.

    Results: Plasma MMP-9 was detectable in all participants, mean 38.9 ng/mL (SD 22.1 ng/mL). Among individuals without reported symptomatic CAD a positive association (p<0.001) was seen, for both men and women, of MMP-9 levels regarding total risk load of eight CV risk factors i.e. blood pressure, dyslipidemia, diabetes, obesity, smoking, alcohol intake, physical activity and fruit and vegetable intake. The association was significant also after adjustment for CRP, and was not driven by a single risk factor alone. In regression models adjusted for age, sex, smoking, alcohol intake and CRP, elevated MMP-9 levels were independently positively associated with systolic blood pressure (p = 0.037), smoking (p<0.001), alcohol intake (p = 0.003) and CRP (p<0.001). The correlation coefficient between MMP-9 and CRP was r = 0.24 (p<0.001).

     

    Conclusions: In a population without reported symptomatic CAD, MMP-9 levels were associated with total CV risk load as well as with single risk factors. This was found also after adjustment for CRP

     

  • 22.
    Garvin, Peter
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Socialmedicin och folkhälsovetenskap. Linköpings universitet, Hälsouniversitetet.
    Nilsson, Lennart
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Filosofiska fakulteten.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Kristenson, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Socialmedicin och folkhälsovetenskap. Linköpings universitet, Hälsouniversitetet.
    Plasma Levels of Matrix Metalloproteinase-9 are Independently Associated With Psychosocial Factors in a Middle-Aged Normal Population2009Inngår i: PSYCHOSOMATIC MEDICINE, ISSN 0033-3174, Vol. 71, nr 3, s. 292-300Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To test the association between psychosocial factors and circulating levels of matrix metalloproteinase-9 (MMP-9) in a normal population sample. Psychosocial factors have been associated with inflammatory markers and are of prognostic significance for coronary artery disease (CAD). The degrading enzyme MMP-9 is upregulated in inflammatory processes and hypothesized to play a role in the rupture of atherosclerotic plaques. Methods: A total of 402 participants (50% women), aged 45 to 69 years, were drawn randomly from a normal population. Psychosocial instruments covered depression (Center for Epidemiological Studies Depression Questionnaire, CES-D), vital exhaustion, hostile affect, cynicism, mastery, self-esteem, sense of coherence (SOC), emotional support, and social integration. Plasma MMP-9 was measured by an enzyme-linked immunosorbent assay method. Linear regression models were adjusted for age, sex, known CAD, rheumatoid arthritis, cancer, cardiovascular risk factors including C-reactive protein and ongoing medication. Results: After full adjustment, there were independent associations of elevated MMP-9 levels with CES-D (+2.9 ng/ml per SD, p=.02), hostile affect (+3.0 ng/ml per SD, p=.02), cynicism (+3.5 ng/ml per SD, p=.006), and SOC (-2.5 ng/ml per SD, p=.046). A principal component analysis extracted three components. The first was mainly extracted from CES-D, vital exhaustion, self-esteem, mastery, and SOC; the second was mainly extracted from hostile affect and cynicism. Both were independently associated with MMP-9 (p=.02, p=.04) when run in the same model. Conclusions: MMP-9 levels were associated with psychosocial factors in a middle-aged normal population sample, independently of traditional risk factors. The findings may constitute a possible link between psychosocial factors and cardiovascular risk.

  • 23.
    Geng, Yong-Jian
    et al.
    University of Texas Houston.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Linking immunity to atherosclerosis: Implications for vascular pharmacology - A tribute to Goran K. Hansson2012Inngår i: Vascular pharmacology, ISSN 1537-1891, E-ISSN 1879-3649, Vol. 56, nr 1-2, s. 29-33Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    For the past decade, we have deepened our understanding of the pathogenesis of atherosclerosis, a chronic arterial disease that causes cardiac and cerebral infarction and peripheral vascular disorders. Because of this extended understanding, more effective strategies for prevention and treatment of this disease are emerging. One of the fundamental mechanisms that lead to progress or regression in atherosclerosis, thus influencing its life-threatening complications, occurs through functional changes in vascular immunity and inflammation. This review briefly summarizes the discoveries in basic and translational sciences in this area and recent advances in clinical medicine against atherosclerotic vascular diseases.

  • 24.
    Goncalves, Isabel
    et al.
    Malmö University Hospital.
    Cherfan, Pierre
    Högland Hospital.
    Soderberg, Ingrid
    Malmö University Hospital.
    Nordin Fredrikson, Gunilla
    Malmö University Hospital.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Effects of simvastatin on circulating autoantibodies to oxidized LDL antigens: relation with immune stimulation markers2009Inngår i: AUTOIMMUNITY, ISSN 0891-6934, Vol. 42, nr 3, s. 203-208Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Statins exert a number of anti-inflammatory and immunomodulatory effects in vitro. However, the immunomodulatory effects in vivo are less clarified. In the present study, we investigated whether simvastatin treatment changed the levels of autoantibodies against specific oxidized LDL (oxLDL) antigens as well as their association with leukocyte activation markers. Eighty volunteers with mild-to-moderate hypercholesterolemia were randomized to either simvastatin 40mg or placebo for 6 weeks. Autoantibodies against apo B peptide antigens, C-reactive protein (CRP) and interleukin (IL)-6 in plasma were determined by ELISA. Subsets of circulating B and T cells were studied by flow cytometry. Simvastatin significantly reduced CRP by 26%, whereas IL-6 remained unchanged. Levels of IgG against the apo B peptide P-240 (amino acids 3586-3605) increased by 16% (p=0.03) in the simvastatin group whereas autoantibody levels to other apo B peptides did not change. At baseline and after 6 weeks, the P-240 IgG levels were significantly correlated with the number of CD57+CD28-CD8+T cells but not to other lymphocyte subsets or inflammatory markers. The P-240 IgG levels after 6 weeks simvastatin therapy was strongly correlated to the relative increase in CD57+CD28-CD8+T cells (p=0.003). Simvastatin treatment induced an increase in autoantibodies against an oxLDL antigen. The effect was related to an expansion of a CD8+T cell subset and may involve an immunostimulation by simvastatin.

  • 25.
    Gredmark, Sara
    et al.
    Karolinska Institutet.
    Jonasson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Van Gosliga, Djoke
    Karilinska Institutet.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Söderberg-Nauclér, Cecilia
    Karolinska Institutet.
    Active cytomegalovirus replication in patients with coronary disease2007Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 41, nr 4, s. 230-234Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives. To study the prevalence of active cytomegalovirus (CMV) infection in patients with stable and unstable conditions of coronary artery disease (CAD). Design. Forty patients with acute coronary syndrome (ACS), 50 patients with stable angina and angiographically verified CAD (SA) and 50 clinically healthy controls were included. Monocytes were isolated from peripheral blood and CMV-RNA expression was determined by a nested RT-PCR assay. CMV IgM and IgG antibodies, interleukin-(IL)-6, IL-10 and CRP were measured in serum. Results. The prevalence of active CMV infection was significantly higher in patients with ACS (15%) and in patients with SA (10%) compared with controls (2%) (p < 0.001). The presence of an active CMV infection was associated with increased serum concentrations of IL-6. Conclusions. Active CMV infection was found to a larger extent in CAD patients than in healthy controls. The data indicate that CAD patients are more susceptible to reactivation of CMV and put new focus on the role of CMV in atherosclerosis.

  • 26.
    Hasib, Lekbira
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Lundberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Zachrisson, Helene
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease2016Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, nr 1, s. 63-77Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ObjectiveRegulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome (ACS), particularly non-ST elevation (NSTE)-ACS. However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease (CAD). Here, we investigated the composition and functional properties of naive (n) and memory (m)Tregs in patients with NSTE-ACS and in patients 6-12months post-ACS. MethodsBased on the expression of CD25, FOXP3, CD127, CD45RA, CD39 and CTLA-4, Tregsubsets were defined by flow cytometry in whole blood or isolated CD4(+) T cells. The functional properties of nTregs and mTregs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide (LPS)-induced cytokine secretion and ultrasound-defined carotid atherosclerosis. ResultsBoth NSTE-ACS and post-ACS patients exhibited reduced levels of nTregs (P&lt;0.001) compared with healthy control subjects, but without compensatory increases in mTregs. Both nTregs and mTregs from patients showed significantly lower replicative rates and impaired capacity to modulate T-cell proliferation and secretion of interferon-gamma and IL-10. The Treg defect was also associated with LPS-induced cytokine secretion and increased burden of carotid atherosclerosis. ConclusionOur results demonstrate a functional and homeostatic Treg defect in patients with NSTE-ACS and also in stabilized patients 6-12months after ACS. Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune-restoring strategies in CAD.

  • 27.
    Hovland, Anders
    et al.
    Nordland Hospital, Norway; University of Tromso, Norway.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Garred, Peter
    Copenhagen University Hospital, Denmark.
    Yndestad, Arne
    National Hospital Norway, Norway; National Hospital Norway, Norway; University of Oslo, Norway.
    Aukrust, Pal
    National Hospital Norway, Norway; National Hospital Norway, Norway; University of Oslo, Norway.
    Lappegard, Knut T.
    Nordland Hospital, Norway; University of Tromso, Norway.
    Espevik, Terje
    Norwegian University of Science and Technology, Norway; Department Cancer Research and Molecular Med, Norway.
    Mollnes, Tom E.
    University of Tromso, Norway; University of Oslo, Norway; Norwegian University of Science and Technology, Norway; Department Cancer Research and Molecular Med, Norway; Nordland Hospital, Norway; National Hospital Norway, Norway; University of Oslo, Norway; University of Tromso, Norway.
    The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis2015Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 241, nr 2, s. 480-494Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, may be of particular interest both with respect to pathogenesis and as therapeutic targets in atherosclerosis. Animal studies indicate that inhibition of C3a and C5a reduces atherosclerosis. In humans modified LDL-cholesterol activate complement and TLRs leading to downstream inflammation, and histopathological studies indicate that the innate immune system is present in atherosclerotic lesions. Moreover, clinical studies have demonstrated that both complement and TLRs are upregulated in atherosclerotic diseases, although interventional trials have this far been disappointing. However, based on recent research showing an intimate interplay between complement and TLRs we propose a model in which combined inhibition of both complement and TLRs may represent a potent anti-inflammatory therapeutic approach to reduce atherosclerosis. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.

  • 28.
    Jonasson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Inflammatoriska markörer hos kvinnor2003Annet (Annet (populærvitenskap, debatt, mm))
  • 29.
    Jonasson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    The possible link between infections and atherosclerosis2007Inngår i: Indian Journal of Medical Sciences, ISSN 0019-5359, E-ISSN 1998-3654, Vol. 61, nr 3, s. 124-126Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    [No abstract available]

  • 30.
    Jonasson, Lena
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Backteman, Karin
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Loss of natural killer cell activity in patients with coronary artery disease2005Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 183, nr 2, s. 316-321Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:: Natural killer (NK) cells are important components of the innate immune system and have a potential role in the regulation of autoimmunity. In the present study, we evaluated the NK cells in patients with coronary artery disease (CAD) and related the findings to clinical and laboratory parameters of the disease. Methods and results:: We studied 45 patients with acute coronary syndrome (ACS), 50 patients with stable angina and angiographically verified CAD (SA) and 50 healthy controls. The distribution of NK cell subsets was determined by flow cytometry and NK cell-mediated cytotoxicity was quantified ex vivo. Both ACS and SA patients had significantly reduced numbers of CD56dim NK cells compared with controls. The patients also exhibited a significant decrease in NK cell activity. The loss in NK cell function was not related to inflammatory activity or metabolic status. Conclusion:: Both stable and unstable conditions of CAD were associated with a redistribution of circulating lymphocytes, comprising a significant reduction of CD56dim NK cells and a concomitant loss of NK cell function. The findings suggest the presence of a persistent immune aberration in CAD patients independent of their clinical setting or systemic inflammatory state. © 2005 Elsevier Ireland Ltd. All rights reserved.

  • 31.
    Jonasson, Lena
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Natural killer cells in coronary artery disease2004Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 4, s. 312-312Artikkel i tidsskrift (Fagfellevurdert)
  • 32.
    Jonasson, Lena
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Guldbrand, Hans
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Primärvården i västra länsdelen.
    Lundberg, Anna K
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Nyström, Fredrik H
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Advice to follow a low-carbohydrate diet has a favourable impact on low-grade inflammation in type 2 diabetes compared with advice to follow a low-fat diet2014Inngår i: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 46, nr 3, s. 182-187Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Inflammation may play an important role in type 2 diabetes. It has been proposed that dietary strategies can modulate inflammatory activity.

    METHODS: We investigated the effects of diet on inflammation in type 2 diabetes by comparing a traditional low-fat diet (LFD) with a low-carbohydrate diet (LCD). Patients with type 2 diabetes were randomized to follow either LFD aiming for 55-60 energy per cent (E%) from carbohydrates (n = 30) or LCD aiming for 20 E% from carbohydrates (n = 29). Plasma was collected at baseline and after 6 months. C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra), IL-6, tumour necrosis factor receptor (TNFR) 1 and TNFR2 were determined.

    RESULTS: Both LFD and LCD led to similar reductions in body weight, while beneficial effects on glycaemic control were observed in the LCD group only. After 6 months, the levels of IL-1Ra and IL-6 were significantly lower in the LCD group than in the LFD group, 978 (664-1385) versus 1216 (974-1822) pg/mL and 2.15 (1.65-4.27) versus 3.39 (2.25-4.79) pg/mL, both P < 0.05.

    CONCLUSIONS: To conclude, advice to follow LCD or LFD had similar effects on weight reduction while effects on inflammation differed. Only LCD was found significantly to improve the subclinical inflammatory state in type 2 diabetes.

  • 33.
    Jonasson, Lena
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Hansson, Göran
    Karolinska Institutet Department of Medicine Solna - Stockholm, Sweden Karolinska Institutet Department of Medicine Solna - Stockholm, Sweden.
    Inflammation och ateroskleros – sista pusselbiten är på plats: Inflammation är en aktör vid ateroskleros: nya fynd kan ge ny måltavla för effektiv läkemedelsterapi2017Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inflammation and atherosclerosis - last piece of the puzzle has fallen into place Inflammation is a major component of atherosclerotic lesions and inflammatory biomarkers can be used to predict cardiovascular disease. Still, it has been unclear whether inflammation is a driving force in atherosclerosis, or merely an epiphenomenon. The recently published results of the CANTOS trial shows that treatment with canacinumab, a monoclonal antibody to the proinflammatory cytokine interleukin-1ß, led to a significantly lower rate of recurrent cardiovascular events, compared to placebo. Thus, it establishes beyond doubt that inflammation is a treatable pathogenetic mechanism in atherosclerosis.

  • 34.
    Jonasson, Lena
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Kristenson, Margareta
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Hjärtinfarkt2019Inngår i: Somatisk sjukdom: biopsykosocialt perspektiv / [ed] Ali Sarkohi, Gerhard Andersson, Lund: Studentlitteratur AB, 2019, Vol. Sidorna 65-91, s. 65-91Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 35.
    Jonasson, Lena
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Tompa, A.
    Department of Microbiology, Ryhov Hospital, Jönköping, Sweden.
    Wikby, A.
    Dept. of Nat. Sci. and Biomedicine, School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Expansion of peripheral CD8+ T cells in patients with coronary artery disease: Relation to cytomegalovirus infection2003Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 254, nr 5, s. 472-478Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives. The nature of the immune response in coronary artery disease (CAD) is not fully defined. One pathogen that has been linked to atherogenesis, cytomegalovirus (CMV). is known to exert strong and long-lasting effects on peripheral T cells. In the present study, we investigated the effect of prior CMV infection on the immune system in CAD patients. Subjects. Patients with stable angina and angiographically verified CAD (n = 43) and clinically healthy controls (n = 69) were included. Methods. The expression of CD57 and CD28 on peripheral CD4+ and CD8+ T cells was evaluated with three-colour flow cytometry. The findings were related to serological markers of inflammation, T-cell activation and CMV seropositivity. Results. An expansion of CD8+ T cells expressing CD57 but lacking CD28 was seen in the patient group. The numbers of CD8+CD57+ and CD8+ CD28- T-cell subsets were independently related to CMV seropositivity (P < 0.001) but also to CAD per se (P < 0.05). Serum concentrations of C-reactive protein (CRP) and soluble interleukin-2 receptor (sIL-2R) were elevated in the patients but not related to CMV or CD8 + T-cell subsets. Conclusion. A pronounced shift in peripheral T-cell homeostasis was observed in CAD patients. Primarily CMV infection but also CAD per se contributed to the expansion of CD8+ T-cell subsets. The T-cell changes were not related to a systemic inflammatory response but should rather be considered as markers of a chronic antigen exposure and/or immunosenescence in CAD.

  • 36.
    Jonasson, Lena
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Wikby, A.
    Dept. of Nat. Sci. and Biomedicine, School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Olsson, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Low serum ß-carotene reflects immune activation in patients with coronary artery disease2003Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 13, nr 3, s. 120-125Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Aim: Low serum levels of antioxidant vitamins are associated with coronary artery disease (CAD). An immunomodulatory effect of antioxidants has been proposed. The aim of the study was to investigate whether an increased immune response in CAD patients was associated with suppressed circulating levels of antioxidant vitamins. Methods and Results: Forty-four men with stable angina and angiographically verified CAD were included as well as 69 healthy controls. T cell subsets in peripheral blood were quantified by 3-colour flow cytometry. C-reactive protein (CRP), soluble interleukin-2 receptor (sIL-2R) and the lipophilic antioxidants a-tocopherol, ß-carotene and lycopene were determined in serum. Compared with controls, patients had signs of an enhanced inflammatory activity assessed by significantly increased levels of CRP, sIL-2R and CD4+CD25+T cell subsets. Patients also had significantly lower ß-carotene and lycopene levels whereas a-tocopherol levels did not differ. The increased inflammatory/immune parameters in patients showed a significant inverse relationship to serum ß-carotene but not to lycopene or a-tocopherol. Conclusions: Low serum ß-carotene in CAD patients reflects activation of the immune system. Inflammation should be considered as an important confounding factor when analysing data on ß-carotene and CAD. © 2003, Medikal Press.

  • 37. Jönsson, S
    et al.
    Bergström, I
    Li, Wei
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson,
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Neutrophils- a potential source for increased serum MMP-9 in coronary artery disease.2009Konferansepaper (Fagfellevurdert)
  • 38.
    Jönsson, Simon
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Bergström, Ida
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Li, Wei
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Nilsson, L
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    NEUTROPHILS - A POTENTIAL SOURCE FOR INCREASED SERUM MMP-9 IN CORONARY ARTERY DISEASE in ATHEROSCLEROSIS SUPPLEMENTS, vol 10, issue 2, pp2009Inngår i: ATHEROSCLEROSIS SUPPLEMENTS, Elsevier Science B.V., Amsterdam. , 2009, Vol. 10, nr 2Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 39.
    Jönsson, Simon
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Kälvegren, Hanna
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Lundberg, A
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Neutrophils but not platelets are a major source of MMP-9 in coronary artery disease in EUROPEAN HEART JOURNAL, vol 31, issue , pp 486-4872010Inngår i: EUROPEAN HEART JOURNAL, Oxford University Press , 2010, Vol. 31, s. 486-487Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 40.
    Jönsson, Simon
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Lundberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Overexpression of MMP-9 and Its Inhibitors in Blood Mononuclear Cells after Myocardial Infarction - Is It Associated with Depressive Symptomatology?2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 8, s. e105572-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Matrix metalloproteinase (MMP)-9 may play a central role in the development and progression of atherosclerosis. Emerging evidence also indicates an association between MMP-9 and depressive symptomatology. Here, we investigated whether expression of MMP-9 and its inhibitors in blood mononuclear cells and plasma were related to depressive symptoms in patients with a recent myocardial infarction (MI). Methods and Results: Blood sampling was performed between 6 and 18 months after MI in 57 patients. Forty-one clinically healthy subjects were included as controls. Gene expression of MMP-9 and its main tissue inhibitors TIMP-1 and -2 were analyzed in freshly isolated or cultured blood mononuclear cells. Corresponding protein levels were assessed in cell supernatants and plasma. In post-MI patients, mRNA levels of MMP-9 and TIMP-1 and -2 were significantly higher than in controls while protein levels in cell supernatants and plasma did not differ between groups. The Center for Epidemiological Studies - Depression (CES-D) scale was used to assess depressive symptomatology. Repeated assessments during the first 18 months after MI showed significantly higher CES-D scores in patients compared with controls. However, there were no relationships between depressive mood and any of the measurements of MMP-9 or TIMPs. Conclusion: Our findings indicate that overexpression of MMP-9 and TIMPs in blood mononuclear cells and elevated depressive symptoms represent two unrelated phenomena after MI.

  • 41.
    Jönsson, Simon
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Lundberg, Anna K
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    The glucocorticoid receptor alpha isoform is overexpressed in blood mononuclear cells from patients with coronary artery disease: Evidence for increased glucocorticoid sensitivityManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Context: Coronary artery disease (CAD) is characterized by low-grade chronic inflammation including leukocyte-derived overexpression of matrix metalloproteinase (MMP)-9 and its tissue inhibitors (TIMPs). The mechanisms behind this overexpression are not clarified but may involve dysregulated glucocorticoid regulation of MMP-9.

    Objective: We hypothesized that the increased expression of MMP-9 and TIMPs in peripheral blood mononuclear cells (PBMCs) from CAD patients was associated with reduced glucocorticoid sensitivity.

    Setting: This was an observational study conducted at the Outpatient Cardiology Clinic at the University Hospital, Linköping, Sweden.

    Participants: CAD patients with a history of non-ST-elevation myocardial infarction were consecutively included. Healthy control subjects were randomly recruited from the Swedish Population Register.

    Main outcome measures: We measured mRNA and protein levels of glucocorticoid receptors (GR)-α and -β in PBMCs in vivo and further investigated the effects of dexamethasone on MMP-9, TIMP, GR-α and -β expression ex vivo.

    Results: The GR-α mRNA levels were markedly increased in PBMCs from CAD patients, whereas GR-β mRNA levels did not differ between patients and controls. Ex vivo, the inhibitory effects of dexamethasone on MMP-9 and TIMP mRNA and protein expression were equal to or slightly higher in patients. Moreover, the dexamethasone treatment resulted in significantly reduced levels of GR-α mRNA in PBMCs.

    Conclusion: In contrast to our original hypothesis, we found evidence for increased glucocorticoid sensitivity in PBMCs from CAD patients. It may be suggested that the overexpression of MMP-9 and TIMPs in patients is associated with a state of relative hypocortisolism, thus contributing to a systemic low-grade inflammation.

  • 42.
    Jönsson, Simon
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Lundberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Kälvegren, Hanna
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Bergström, Ida
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Szymanowski, Aleksander
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris2011Inngår i: PLOS ONE, ISSN 1932-6203, Vol. 6, nr 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: There is a growing interest for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in plasma as novel biomarkers in coronary artery disease (CAD). We aimed to identify the sources of MMP-8, MMP-9, TIMP-1 and TIMP-2 among peripheral blood cells and further explore whether gene expression or protein release was altered in patients with stable angina pectoris (SA). Methods: In total, plasma MMP-9 was measured in 44 SA patients and 47 healthy controls. From 10 patients and 10 controls, peripheral blood mononuclear cells (PBMC) and neutrophils were isolated and stimulated ex vivo. MMPs, TIMPs and myeloperoxidase were measured in plasma and supernatants by ELISA. The corresponding gene expression was measured by real-time PCR. Results: Neutrophils were the dominant source of MMP-8 and MMP-9. Upon moderate stimulation with IL-8, the neutrophil release of MMP-9 was higher in the SA patients compared with controls (p andlt; 0.05). In PBMC, the TIMP-1 and MMP-9 mRNA expression was higher in SA patients compared with controls, p andlt; 0.01 and 0.05, respectively. There were no differences in plasma levels between patients and controls except for TIMP-2, which was lower in patients, p andlt; 0.01. Conclusion: Measurements of MMPs and TIMPs in plasma may be of limited use. Despite similar plasma levels in SA patients and controls, the leukocyte-derived MMP-9 and TIMP-1 are significantly altered in patients. The findings indicate that the leukocytes are more prone to release and produce MMP-9 in symptomatic and angiographically verified CAD-a phenomenon that may have clinical implications in the course of disease.

  • 43.
    K Hansson, Goran
    et al.
    Karolinska Institute.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    The Discovery of Cellular Immunity in the Atherosclerotic Plaque2009Inngår i: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, ISSN 1079-5642, Vol. 29, nr 11, s. 1714-1717Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It is now generally accepted that atherosclerosis is an inflammatory/immune disease triggered by LDL accumulation in the artery wall. When discovering T cells and the molecular components of a cellular immune response, we proposed that atherosclerosis is an inflammatory process with an autoimmune component. This notion was met with general skepticism but has gained support from experimental and clinical studies. Here we describe some of the early studies that helped developing this concept.

  • 44.
    Kälvegren, Hanna
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US. University of Örebro.
    Jonsson, Simon
    Jonasson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Release of matrix metalloproteinases-1 and-2, but not-9, from activated platelets measured by enzyme-linked immunosorbent assay2011Inngår i: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 22, nr 8, s. 572-578Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Matrix metalloproteinases (MMPs), in particular MMP-9, have been introduced as novel biomarkers in coronary artery disease. Activated platelets are considered to be a major source of the highly elevated levels of MMPs that are detected in serum compared to plasma. The aim of this study was to clarify if activated platelets release MMPs-1, -2 and -9 as measured by enzyme-linked immunosorbent assays (ELISA). Isolated platelets (separated by several procedures) or platelet-rich plasma (PRP) were stimulated by collagen, thrombin or the TLR2 agonist Pam(3)CSK(4). The concentrations of MMPs-1,-2 and -9 in supernatants were determined by ELISA. In addition, a MMP-9 enzyme activity assay was used as well as immunofluorescent staining of MMPs-1,-2 and 9 in platelets. Isolated platelets stimulated by collagen, thrombin or Pam(3)CSK(4) released significant amounts of MMP-1 to the supernatant measured as either pro- or total-MMP-1. However, there was no detectable release of MMP-2 or -9 from isolated platelets. Collagen-stimulated platelets in PRP released MMP-2, but not -9. Before stimulation; platelets were positive for MMPs-1 and -2, but not -9, as assessed by immunofluorescence. Acting as positive controls, neutrophils were found to release significant amounts of MMP-9. Our findings indicate that activated platelets may be a major source of MMP-1 and to a minor extent MMP-2, in peripheral blood. However, in contrast to what has been argued in previous literature, platelets appear to be only negligible contributors to circulating MMP-9.

  • 45.
    Lappegard, Knut T.
    et al.
    Nordland Hospital, Norway; University of Tromso, Norway.
    Gaffed, Peter
    Copenhagen University Hospital, Denmark.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Espevik, Terje
    Norwegian University of Science and Technology, Norway.
    Aukrust, Pal
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Yndestad, Arne
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Mollnes, Tom E.
    University of Tromso, Norway; Norwegian University of Science and Technology, Norway; University of Oslo, Norway; Nordland Hospital, Norway; Oslo University Hospital, Norway.
    Hovland, Anders
    Nordland Hospital, Norway; University of Tromso, Norway.
    A vital role for complement in heart disease2014Inngår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 61, nr 2, s. 126-134Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors, emerging evidence points to an association between the complement system and heart diseases. Thus, complement seems to be important in coronary heart disease as well as in heart failure, where several studies underscore the prognostic importance of complement activation. Furthermore, patients with atrial fibrillation often share risk factors both with coronary heart disease and heart failure, and there is some evidence implicating complement activation in atrial fibrillation. Moreover, Chagas heart disease, a protozoal infection, is an important cause of heart failure in Latin America, and the complement system is crucial for the protozoa-host interaction. Thus, complement activation appears to be involved in the pathophysiology of a diverse range of cardiac conditions. Determination of the exact role of complement in the various heart diseases will hopefully help to identify patients that might benefit from therapeutic complement intervention.

  • 46.
    Li, Wei
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Johnson, Henrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Yuan, Xi-Ming
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet.
    7beta-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destabilization2009Inngår i: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 43, nr 11, s. 1072-1079Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Peripheral natural killer (NK) cells are reduced in patients with coronary artery disease and highly susceptible to apoptosis induced by oxidized lipids including 7beta-hydroxycholesterol (7betaOH) in vitro. The present study aimed to further explore the mechanisms behind 7betaOH-mediated cytotoxicity to human NK cells. Human NK cells were purified and treated with 7betaOH in different concentrations and times. Cell death, lysosomal and mitochondrial permeabilization and reactive oxygen species (ROS) production were then analysed. The 7betaOH induced time and dose dependent apoptosis and necrosis in human NK cells, which was preceded by loss of lysosomal integrity and enhanced ROS production. At later time points, the mitochondrial membrane permeability in 7betaOH-treated cells was significantly increased. The findings indicate that 7betaOH induces human NK cell death through early lysosomal permeabilization and consequent oxidative stress. The data further suggest that 7betaOH may induce immune disturbances in clinical settings such as atherosclerosis.

  • 47.
    Li, Wei
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Johnson, Henrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Yuan, Ximing
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    7-beta-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destalization.2009Konferansepaper (Fagfellevurdert)
  • 48.
    Li, Wei
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Johnson, Henrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Yuan, Xi-Ming
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    7ß-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destabilization2009Inngår i: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 43, nr 11, s. 1072-1079Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Peripheral natural killer (NK) cells are reduced in patients with coronary artery disease and highly susceptible to apoptosis induced by oxidized lipids including 7beta-hydroxycholesterol (7betaOH) in vitro. The present study aimed to further explore the mechanisms behind 7betaOH-mediated cytotoxicity to human NK cells. Human NK cells were purified and treated with 7betaOH in different concentrations and times. Cell death, lysosomal and mitochondrial permeabilization and reactive oxygen species (ROS) production were then analysed. The 7betaOH induced time and dose dependent apoptosis and necrosis in human NK cells, which was preceded by loss of lysosomal integrity and enhanced ROS production. At later time points, the mitochondrial membrane permeability in 7betaOH-treated cells was significantly increased. The findings indicate that 7betaOH induces human NK cell death through early lysosomal permeabilization and consequent oxidative stress. The data further suggest that 7betaOH may induce immune disturbances in clinical settings such as atherosclerosis.

  • 49.
    Li, Wei
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Kornmark, Louise
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Forssell, Claes
    Linköpings universitet, Institutionen för medicin och hälsa, Kärlkirurgi. Linköpings universitet, Hälsouniversitetet.
    Yuan, Ximing
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Cathepsin L is significantly associated with apoptosis and plaque destabilization in human atherosclerosis2009Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 202, nr 1, s. 92-102Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Human atherosclerotic lesions overexpress elastolytic and collagenolytic cathepsins with unclear pathological implications. The aim of this study was to investigate the relationship among expression of cathepsin L. macrophage apoptosis in coronary artery disease (CAD) patients, clinical symptoms and plaque severity Of human carotid atheroma.

    Methods and results: Quantitative immunohistochemical analysis of human carotid atherosclerotic lesions (n = 49) showed that expression of lysosomal cathepsin L was significantly increased in atherosclerotic plaques with formation of the necrotic core and rupture of the cap. In those Plaques, cathepsin L was associated mainly with CD68-positive macrophages, whereas significant lower levels of smooth muscle cell actin were detected. The expression of cathepsin L in these plaques was also correlated with apoptosis and the stress protein ferritin. Plaques from symptomatic patients showed greater increased levels of cathepsin L than those front asymptomatic patients. Human monocyte-derived macrophages from CAD patients (n = 7) showed significantly higher levels of cathepsin L, cellular lipids and apoptosis versus cells from matched healthy donors (n = 7). 7Beta-hydroxycholesterol significantly enhanced cathepsin L in cells from healthy donors but not in Cells from CAD patients. Moreover. macrophage apoptosis was significantly correlated with expression of cathepsin L in cell nuclei and membranes.

    Conclusion: The results Suggest that cathepsin L is involved in death of macrophages necrotic Core formation and development of atherosclerotic plaque instability. Macrophage lysosomal cathepsin L and related apoptosis may be potential targets for modulation or imaging of vulnerable plaques in human atherosclerosis.

  • 50.
    Li, Wei
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Lidebjer, Caroline
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet.
    Yuan, Ximing
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi.
    Szymanowski, Aleksander
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Backteman, Karin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Ernerudh, Jan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk immunologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk immunologi och transfusionsmedicin.
    Leanderson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Östergötlands Läns Landsting, Smärt- och yrkesmedicinskt centrum, Yrkes- och miljömedicinskt centrum.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Kardiologi.
    Swahn, Eva
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Jonasson, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    NK cell apoptosis in coronary artery disease. Relation to oxidative stress2008Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 199, nr 1, s. 65-72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Natural killer (NK) cells, key elements in initiation and modulation of immune responses, were recently found to be reduced in coronary artery disease (CAD). To clarify mechanisms behind this reduction, we here investigated NK cell apoptosis in CAD patients. Since oxidative stress has been linked to NK cell apoptosis, we related the findings to oxidative stress in vivo and evaluated the ex vivo susceptibility of NK cells to oxidized lipids. Methods and results: The number of apoptotic NK cells in peripheral blood was significantly increased in CAD patients compared to controls. Purified NK cells from CAD patients also showed a higher rate of spontaneous apoptosis ex vivo. Dose- and time-dependent effects of oxidized LDL and 7β-hydroxycholesterol (7βOH) on apoptosis and ROS production were determined in NK cells from blood donors. Thereafter, purified NK cells from CAD patients and healthy controls were exposed to the oxidized lipids in a paired design. NK cells from patients were more susceptible to apoptosis induced by oxidized LDL, in particular 7βOH, compared to cells from controls. Plasma measurements of LDL protein oxidation and lipid peroxidation did not show any differences between patients and controls. On the other hand, plasma carotenoids were significantly decreased in patients and inversely correlated to NK cell apoptosis rate. Conclusion: The rate of spontaneous NK cell apoptosis was increased in CAD patients. Although NK cells in CAD patients were more sensitive to oxidized lipids ex vivo, indicating a mechanism contributing to the reduced NK cell activity in CAD, the data could not verify an obvious link between NK cell apoptosis and increased oxidative stress in vivo. © 2007 Elsevier Ireland Ltd. All rights reserved.

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