The Vascular Immunology Group:
Anna Lundberg, PhD, Principal Research Engineer
Lekbira Hasib, PhD, Principal Research Engineer
Ida Bergström, Simon Jönsson, Aleksander Szymanowski and
Mireille Rydén, PhD Students
Immune perturbations in coronary artery disease
The progression of atherosclerotic disease, including episodes of plaque instability, may be due to an imbalance between inflammatory and antiinflammatory actions. The mechanisms behind this imbalance are far from clarified. So far, we have evidence for a perturbed immune homeostasis in patients with coronary artery disease (CAD). The changes involving phenotypic shifts of NK cells, CD8+ T cells and regulatory T cells (T regs) in peripheral blood, may represent a premature aging of the immune system. It may also indicate a failure to suppress inflammatory activity. CAD patients exhibit both a dysregulated cortisol secretion and an enhanced inflammatory and proteolytic activity in blood, the latter exemplified by increased expression of matrix metalloproteinase (MMP)-9 in blood mononuclear cells. By understanding the underlying causes and consequences of the perturbed immune system, we can learn how to restore it and hopefully thereby prevent the complications of disease.
A brief description of our current projects is given below:
- High cortisol levels and a flatter cortisol diurnal rhythm are associated with a proinflammatory state in CAD patients. In this project, we study the effects of cortisol on leukocyte function in CAD patients, focusing on glucocorticoid sensitivity and synthesis/release of cytokines, MMP-9 and the endogenous inhibitor of MMP-9 (TIMP-1) (Simon Jönsson, PhD project).
- CD8+CD56+ T cells accumulate in peripheral blood of CAD patients and are potent producers of interferon (IFN)-. In this project, we evaluate whether this phenomenon is due to immunosenescence. Furthermore, the capacity of cortisol and glucocorticoid-induced protein annexin-1 to counterbalance the proinflammatory actions of CD8+CD56+ T cells is investigated (Ida Bergström, PhD project).
- Immune perturbations in CAD also include a reduction of circulating NK cells and in parallel, an increased susceptibility of NK cell apoptosis is observed. Here, we investigate the reconstitution of NK cells in vivo and ex vivo in CAD patients and also aim to identify surrogate plasma markers of NK cell turnover. Markers of apoptosis may represent such surrogate markers. This latter aspect will be explored in various patient cohorts, e.g. by studying the effect of cardiac resynchronization therapy on NK cells and NK cell surrogate markers in CAD patients with heart failure (Aleksander Szymanowski, PhD project).
- Like NK cells, T regs may be important for the maintenance of immune homeostasis. In a separate project, the distribution and function of naïve and memory Tregs are studied in CAD patients.
- In population-based studies, chronic psychosocial stress is associated with a flatter cortisol rhythm and higher levels of inflammatory markers (CRP, IL-6) and MMP-9. Our preliminary findings indicate that chronic stress, as assessed by depressive mood and low mastery, is increased in CAD patients compared with healthy controls. In an on-going study, psychosocial stress in CAD patients is evaluated in relation to dysfunctional cortisol response and immune perturbations. On the basis of the results, an interventional trial using mindfulness-based stress reduction in CAD patients will be designed (Oskar Lundgren, PhD project).
- Carotenoids may have important immunomodulatory effects and in plasma, the levels of carotenoids are inversely associated with inflammatory and proteolytic markers, in particular MMP-9. In an interventional trial, we are planning to study the effects of a 12-week carotenoid-rich diet on cytokine and MMP-9 expression in blood mononuclear cells of CAD patients (collaboration with Örebro University).
Lena Jonassons publications in DiVA (publication database).
Name: Lena Jonasson
Position: Professor in Cardiology
Department: Department of Medical and Health Sciences
Division: Cardiovascular Medicine
Division of Cardiovascular Medicine
Department of Medical and Health Sciences
SE-581 85 LINKÖPING
Last updated: 2014-11-06