Heart failure, the clinical syndrome of end-stage cardiac disease of diverse etiologies, is a major cause of morbidity and mortality. In evolving heart failure, multiple compensatory actions are triggered in order to maintain cardiac output, among which is activation of the sympathetic nervous system, the renin-angiotensin system, as well as a number of autocrine/paracrine factors synthesized in myocardial tissue. These compensatory actions also reflect in alterations of cardiac structure, collectively called cardiac remodeling. The most important structural alterations are cardiac myocyte hypertrophy and myocardial fibrosis. Although cardiac remodeling may initially balance loss of contractile force, the continuum of these structural alterations often feeds into vicious circles leading to progression of cardiac dysfunction.
The major goal of the research group is to uncover the mechanisms of progressive fibrosis and based on such new knowledge develop novel pharmacologic treatment that may halt further fibrosis. Fibrosis is the increased generation of connective tissue and deposition of collagen in organs affected by chronic disease. Fibrosis itself is an important contributing factor to organ failure in several diseases, e.g. heart failure, chronic kidney disease and interstitial lung diseases. Fibrosis may also reduce the efficacy of chemotherapy of certain types of cancer. Cardiac fibrosis is an important cause of arrhythmias and may contribute to both systolic dysfunction (e.g. ischemic heart disease) and diastolic dysfunction (e.g. hypertensive heart disease or myocardial dysfunction associated with metabolic syndrome and type 2 diabetes mellitus). The current major focus of the research group is the matricellular CCN proteins, a family of secreted proteins involved in tissue repair mechanisms. Several CCN family members are verified disease targets in the mechanisms of fibrosis. Yet, our knowledge on how CCN proteins work on cells and orchestrate intracellular signal mechanisms is still poorly understood.
The research group consists of an interdisciplinary team of molecular biologists, cell biologists, and medical doctors. The research is covering a wide spectrum from biochemistry, cell biology, to physiologic and pathophysiologic studies of genetically engineered laboratory animals.