Delving into pyroptosis in atherosclerosis: role, mechanisms and therapeutic opportunities

Atherosclerosis is a chronic inflammatory condition that represents the primary culprit of multiple cardiovascular diseases. Pyroptosis is a modality of programmed cell death that is elicited by, and can in return amplify, inflammatory reactions, and thus has attracted increasing attention for its proatherogenic role. Studies have gathered a body of evidence that supports pyroptosis as an important mechanism that drives atherosclerosis pathogenesis and progression. In this review, we present a comprehensive overview of the current state, particularly the recent progress, in understanding pyroptosis of endothelial cells, macrophages and vascular smooth muscle cells and their role in atherosclerosis. We summarize the pathways that mediate cell pyroptosis and the molecular mechanisms that are mobilized by a diversity of proatherogenic risk factors and pathological conditions to stimulate such pyroptosis pathways. We also discuss the ongoing interest in targeting the pyroptosis-driving pathways and mechanisms as therapeutic strategies to intervene atherosclerosis and related cardiovascular diseases.