Public Defence: Negar Shahini - Immunology
M.Sc. Negar Shahini at Institute of Clinical Medicine will be defending the thesis Dysregulation of the complement system in cardiac disease - clinical and experimental studies for the degree of PhD.
Photo: Øystein Horgmo, UiO
Trial Lecture - time and place
See Trial Lecture.
- First opponent: Professor Seppo Meri, Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, Finland
- Second opponent: Assistant Professor Ilze Bot, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands
- Third member of the adjudication committee: Professor Alessandro Cataliotti, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor Kåre Olav Stensløkken, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo
Arne Yndestad, Group leader, PhD, Research Institute of Internal Medicine, Oslo University Hospital
Heart failure (HF) is an important and increasing cause of cardiovascular morbidity and mortality. The development of HF is characterized by chronic low-grade activation of the immune system; however, the exact underlying molecular mechanisms remain to be understood. The complement system, a central arm of the innate immune system, is activated in HF. My thesis focuses on the role of different complement system components in both HF and severe symptomatic aortic stenosis (AS) and their associations with severity of the disease. We hypothesized that complement activation in these patients is mediated through changed levels of amplification loop components such as promoters of the alternative pathway (AP) i.e. properdin and factor D (FD), the AP inhibitor factor H (FH) and FB, an essential component for entire system activation. In addition, we investigated the role of C3 and CD14, bottleneck molecules of pattern recognition systems, in progression of cardiac remodelling in mouse model of angiotensin II-induced cardiac pressure overload.
Taken together, our main findings were that HF patients had significantly increased circulating levels of FD, TCC, and FB with particularly high levels in patients with the more advanced disease. Moreover, decreased circulating levels of FH and properdin were associated with adverse clinical outcome in these patients. Our research has demonstrated that patients with symptomatic AS have increased complement activation indicated by elevated circulating levels of TCC. Notably, elevated levels of FB were significantly associated with increased risk of major cardiovascular events and all-cause mortality. Furthermore, our murine model revealed that deficiency in C3 and CD14 did not affect cardiac remodelling in cardiac pressure overload model. Our findings suggest that while C3 and CD14 might not be directly involved in cardiac remodelling, essential complement system components are elevated during symptomatic AS and chronic HF, and FB could potentially represent a novel marker for risk stratification in these patients.
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