Pyroptosis: A pro-inflammatory type of cell death in cardiovascular disease

Pyroptosis is a pro-inflammatory type of regulated cell death (RCD) characterized by gasdermin D (GSDMD)-mediated membrane pore formation, cell swelling and rapid lysis, followed by the massive release of pro-inflammatory mediators such as interleukin-1β and interleukin-18. There are two main pathways of pyroptosis: the caspase-1-mediated canonical pathway and the caspase-4/5/11-mediated noncanonical pathway. However, the caspase-3-gasdermin E (GSDME) pathway and caspase-8-GSDMD pathway also induce pyroptosis. Pyroptosis can not only cause local inflammation but also lead to amplification of the inflammatory response. Recent studies have suggested that pyroptosis is closely related with cardiovascular disease (CVD); for example, in atherosclerosis, myocardial infarction, ischemia-reperfusion injury, heart failure, coronary calcification and aortic aneurysm, study results have promoted the development of inhibitors targeting the components related to pyroptosis, and some agents have been clinically proven to have cardiovascular benefits. In this review, we summarize emerging evidence to discuss the progressive understanding of pyroptosis and the pathways, effect and effectors of pyroptosis, as well as the role of pyroptosis in CVD. Additionally, we summarize pyroptosis-related pathway inhibitors and classic cardiovascular drugs targeting pyroptosis.