cFLIPL alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis

Abstract Alleviating myocardial ischemia‐reperfusion injury (MIRI) plays a critical role in the prognosis and improvement of cardiac function following acute myocardial infarction. Pyroptosis is a newly identified form of cell death that has been implicated in the regulation of MIRI. In our study, H9c2 cells and SD rats were transfected using a recombinant adenovirus vector carrying cFLIP L , and the transfection was conducted for 3 days. Subsequently, H9c2 cells were subjected to 4 h of hypoxia followed by 12 h of reoxygenation to simulate an in vitro ischemia‐reperfusion model. SD rats underwent 30 min of ischemia followed by 2 h of reperfusion to establish an MIRI model. Our findings revealed a notable decrease in cFLIP L expression in response to ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) injuries. Overexpression of cFLIP L can inhibit pyroptosis, reducing myocardial infarction area in vivo, and enhancing H9c2 cell viability in vitro. I/R and H/R injuries induced the upregulation of ASC, cleaved Caspase 1, NLRP3, GSDMD‐N, IL‐1β, and IL‐18 proteins, promoting cell apoptosis. Our research indicates that cFLIP L may suppress pyroptosis by strategically binding with Caspase 1, inhibiting the release of inflammatory cytokines and preventing cell membrane rupture. Therefore, cFLIP L could potentially serve as a promising target for alleviating MIRI by suppressing the pyroptotic pathway.