Fibrosis is marked by excessive deposition of extracellular matrix and uncontrolled formation of connective tissue, both leading to morphologic changes that impair heart function. DZHK investigators at the Munich partner site have identified premature senescence of myofibroblasts as novel anti-fibrotic mechanism in the heart. Their findings have been published in the Journal of the American College of Cardiology.
The research team led by Antonio Sarikas from the Institute of Pharmacology and Toxicology at Technische Universität München provided several lines of evidence for an essential role of non-age-related premature senescence in restraining cardiac fibrosis. By using different animal models of cardiac diseases, together with human heart biopsies, they showed that myofibroblasts undergo premature senescence in the course of fibrogenesis. Genetic inactivation of the cellular senescence program resulted in aggravated fibrosis and cardiac dysfunction. In contrast, heart-specific induction of senescence limited fibrosis and had cardioprotective effects.
Collectively, this study establishes premature senescence of myofibroblasts as essential anti-fibrotic mechanism and potential therapeutic target in myocardial fibrosis.