Cardiac fibrosis is a hallmark of pathogenic condition in the heart and promotes its dysfunction. In the process of fibrogenesis, physiological structure of the myocardium is replaced by an exaggerated accumulation of stromal cells and extracellular matrix components in the tissue. It has been recognized that local and systemic inflammation represent important pathogenic triggers of fibrotic processes in the heart.
Our research is focused on understanding how heart-specific and heart non-specific autoimmune responses contribute to these pathogenic processes. On cellular level, we investigate 1) a cross-talk between CD4+ T lymphocytes, myeloid cells and microvascular endothelial cells in induction of cardiac inflammation and 2) impact of inflammatory cells and inflammatory mediators on pathogenic activation of cardiac fibroblasts. On molecular level, we study 1) interplay between TGF-beta, Wnt and angiotensin II in the process of cardiac fibrogenesis and 2) cardioprotective aspects of TNF-alpha signaling. Furthermore, we are interested in the role of exosomes in intercellular communication. In our research we are using 1) in vivo mouse models of experimental autoimmune myocarditis and rheumatoid arthritis and 2) in vitro models of various primary mouse and human cardiac cells and 3D model of human cardiac microtissues.
By using these preclinical approaches, we aim to elucidate critical immune-mediated mechanisms controlling development of cardiac fibrosis and heart failure. We believe that outcomes of our research will contribute to better understanding the nature of immunofibrotic heart diseases and to development of novel treatment strategies.