Pyroptosis is an inflammatory form of programmed cell death, distinct from apoptosis, necroptosis, and ferroptosis, and is primarily mediated by gasdermin proteins and inflammatory caspases. Recent advances highlight the central role of pyroptosis in the pathogenesis and progression of a spectrum of cardiovascular diseases, including myocardial infarction, myocarditis, heart failure, atherosclerosis, hypertension, and cardiac arrhythmias. Activation of inflammasomes and the subsequent cleavage of gasdermins drive cell membrane pore formation, leading to the release of interleukin-1β (IL-1β), interleukin-18 (IL-18), and other pro-inflammatory mediators, amplifying tissue injury and sterile inflammation. Both experimental and clinical evidence reveal that targeting key molecules in the pyroptotic pathway, such as NLRP3 inflammasome, caspase-1, and gasdermin D, can attenuate myocardial injury, inhibit adverse cardiac remodeling, and stabilise atherosclerotic plaques. This review systematically summarises the current understanding of the molecular mechanisms of pyroptosis in cardiovascular pathology, details its disease-specific roles, and discusses translational and therapeutic perspectives. Modulating pyroptosis may provide new opportunities for the diagnosis, risk stratification, and treatment of cardiovascular diseases.
Niu et al. (Mon,) studied this question.