Different forms of cardiomyocyte death in post-myocardial infarction ventricular remodeling: mechanisms and therapeutic strategies.

Myocardial infarction (MI) is one of the leading causes of heart failure and cardiovascular mortality worldwide, with post-infarction ventricular remodeling serving as a central pathophysiological mechanism driving the progression toward heart failure, a process that markedly impairs long-term quality of life and contributes to adverse clinical outcomes. Recent studies have gradually elucidated the distinct and overlapping roles of multiple forms of cardiomyocyte death in this process, forming a complex network of programmed cell death; following MI, cardiomyocytes undergo various modes of death including necrosis, apoptosis, as well as more recently identified forms such as ferroptosis and pyroptosis, all of which collectively contribute to ventricular remodeling and the development of heart failure. For instance, ferroptosis, mediated by iron-dependent lipid peroxidation, is markedly elevated after ischemia-reperfusion injury, and inhibition of Glutathione Peroxidase 4 (GPX4) exacerbates plasma membrane rupture, thereby accelerating ventricular wall thinning and left ventricular dilation. Pyroptosis, which relies on activation of the (NOD-like receptor family pyrin domain containing 3-Cysteine-aspartic protease 1-Gasdermin D) NLRP3/caspase-1/GSDMD pathway, leads to the release of inflammatory cytokines, intensifies the local inflammatory microenvironment, and promotes myocardial fibrosis and electrophysiological remodeling. This review systematically summarizes the molecular mechanisms, interplay, and recent advances regarding different forms of cardiomyocyte death in post-MI ventricular remodeling, with particular emphasis on potential therapeutic strategies targeting specific cell death modalities, aiming to provide a novel theoretical foundation and clinical perspectives for optimizing cardioprotection after myocardial infarction.