Abstract
BACKGROUND: Inflammation plays a pivotal role in modulating the pathophysiological progression of myocardial injury and the subsequent repair and remodeling of the infarcted myocardium. Cathepsin B, a member of the cysteine protease family, has been recognized for its ability to initiate various signaling cascades essential to inflammatory processes. This study aims to investigate whether cathepsin B influences cardiomyocyte survival under inflammatory conditions. METHODS: Mice were randomly divided into four groups (n = 6 per group) based on whether they received an intraperitoneal injection of Ca-074 Me (50 mg/kg) and whether myocardial ischemia/reperfusion (I/R) surgery was performed. RESULTS: The cathepsin B-specific inhibitor Ca-074 Me significantly attenuated myocardial infarction caused by I/R in vivo and reduced hypoxia-induced cardiomyocyte apoptosis in vitro. Mechanistically, Ca-074 Me appeared to inhibit caspase-3 signaling, thereby mitigating cardiomyocyte apoptosis under chemical hypoxia induced by cobalt chloride or physical oxygen deprivation. CONCLUSION: Targeted inhibition of cathepsin B may represent an innovative strategy for the amelioration of myocardial injury.