Cross-regulation of autophagy and pyroptosis: a new perspective on the inflammatory microenvironment of atherosclerosis.

The pathogenesis of atherosclerosis (AS) is a chronic disease marked by inflammation, and there are intimate associations with various forms of programmed cell death (PCD). Recently, the mechanisms of pyroptosis and autophagy in AS have attracted much attention. Pyroptosis is a form of PCD mediated by inflammasomes, which worsens local inflammatory responses by releasing proinflammatory factors (e.g., IL-18 and IL-1β) and favors plaque instability and thrombosis. Autophagy is a process that helps to keep cells healthy by breaking down damaged cell structures and abnormal proteins. Mitophagy, a specialized form of autophagy, is of major importance to redox homeostasis and the regulation of inflammation. However, the dysregulation of autophagy may disturb the cellular homeostasis, which then accelerates the progression of AS. Studies have found a complex mutual regulation between pyroptosis and autophagy. Autophagy can block the occurrence of pyroptosis by degrading the components of such as NLRP3. The inflammatory mediators released during pyroptosis may cause the disorder of autophagy, which aggravates the cell death and inflammatory response. The disorder of autophagy will also promote pyroptosis' occurrence and progress. Both of them play a vital role in AS. This study is mainly focused on clarifying the relationship and molecular mechanism between pyroptosis and autophagy in the context of AS. These findings pave the way for new avenues for understanding its pathogenesis and potentially therapeutic decision-making.