Research progress on the role of GSDMD-mediated pyroptosis in athero-sclerosis
More and more studies have shown that the occurrence of atherosclerosis is closely related to pyroptosis,especially gasdermin D(GSDMD)-mediated pyroptosis.In atherosclerosis,inflammatory cells such as macrophages,vascular endothelial cells,and vascular smooth muscle cells undergo pyroptosis,leading to plaque rupture and thrombosis,and finally to acute cor-onary syndrome.In the development of atherosclerosis,arterial wall endothelial injury and lipid deposition are the main initia-ting factors,which activate Caspase-1 and Caspase-11/4/5,respectively,and in turn cause the cleavage of the GSDMD protein and mediate classical and non-classical cell pyroptosis.The N-terminus of the GSDMD protein migrates to the cell membrane and oligomerizes to form pores through which the inflammatory factors IL-1β and IL-18 are released into the interstitium.The release of inflammatory factors further promotes the death of intravascular cells,after which their contents,cytokines,and proteases enter the extracellular matrix,aggravating the local inflammatory response,leading to atherosclerotic plaque rupture and cardiovascular disease.Based on the above mechanism,the development of drugs that directly target GSDMD and signal molecules in the pyroptosis signaling pathway induced by GSDMD,such as inflammasomes,Caspase-1,IL-1β,and IL-18,provides a theoretical basis and new ideas for the treatment of atherosclerosis.
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