Abstract 20201: Activation of DNA Damage Response and Cellular Senescence in Cardiac Fibroblasts Limit Cardiac Fibrosis After Myocardial Infarction

Introduction: Activation and proliferation of cardiac fibroblasts (CFs) play an important role in the formation of cardiac fibrosis after myocardial infarction (MI). Molecular mechanisms that promote these are well studied and considered as therapeutic targets for preventing excessive cardiac fibrosis. However, the molecular mechanisms by which the activation of CFs is “extinguished” and returns to inactive, non-proliferative state after MI remain unclear. Recent reports suggest that activation of DNA damage response (DDR) and cellular senescence in CFs limits fibrosis of various tissues. Methods and Results: We generated a mice model of MI and found that the number of proliferating CFs was increased up to day 4 but gradually decreased and returned to the basal level at day 7 after MI. In contrast, the number of the CFs positive for γH2AX, an active DDR marker, and senescence-associated beta-galactosidase-positive CFs were increased up to day 7 after MI, suggesting that cellular senescence occurred in CFs...