Targeting pyroptosis to treat aortic aneurysms: From mechanism to drug discovery (Review).

Pyroptosis is a lytic and highly inflammatory type of programmed cell death that is mediated primarily by members of the gasdermin (GSDM) protein family. Upon activation by inflammatory stimuli or danger signals, GSDMs are cleaved to release N‑terminal fragments that oligomerize and form pores in the plasma membrane. This disrupts cellular integrity, resulting in osmotic lysis and the release of potent proinflammatory cytokines, such as interleukin (IL)‑1β and IL‑18. The progression of an aortic aneurysm (AA) is driven by complex pathophysiological processes, with the loss of vascular smooth muscle cells and sustained vascular inflammation being central to disease pathogenesis. Emerging evidence indicates that pyroptosis markedly contributes to AA development by amplifying inflammatory activation and promoting cellular disintegration within the aortic wall. Further preclinical evidence has demonstrated that pharmacological inhibition of key pyroptosis signaling pathways effectively attenuates AA formation in murine models, underscoring its promising therapeutic potential. The present review summarizes the molecular mechanisms of pyroptosis, highlights its pathophysiological role in AAs and discusses novel therapeutic strategies targeting pyroptosis for the treatment of AAs.