S100A9 and Myocardial fibrosis: Experimental Validation Findings S100A8/A9 was confirmed to be a key initiator molecule of I/R by S100A9 knockdown and overexpression experiments in animals, and in mice with a total deficiency of S100A9 after MI/RI, infarct size was significantly reduced, cardiac contractile function was improved, CM death was significantly reduced, and myocardial fibrosis was attenuated, suggesting that S100A9 increases the degree of myocardial ischemia-reperfusion injury (39, 43).