NLRP3-mediated pyroptosis in cardiovascular disease: from molecular mechanisms to therapeutic targets

FIGURE 1. Xu, Q. (2026). NLRP3-Mediated Pyroptosis in Cardiovascular Diseases. Created in BioRender. https://BioRender.com/et5s1au.

FIGURE 2. Schematic diagram illustrating the mechanism of pyroptosis. This figure illustrates the classical and non-classical signaling pathways of pyroptosis. In the classical pathway, pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) activate pattern recognition receptors (such as TLR4/NF-κB), thereby upregulating the transcriptional expression of the NLRP3 inflammasome, pro-IL-1β, and pro-IL-18. Subsequently, ASC and pro-caspase-1 are recruited; activated caspase-1 cleaves GSDMD to generate the pore-forming GSDMD-N fragment, inducing cell membrane perforation and the release of cellular contents, and also cleaves pro-IL-1β and pro-IL-18 into their mature forms, IL-1β and IL-18, thereby exacerbating the inflammatory response. In the non-classical pathway, intracellular LPS directly activates caspase-4/5 (mouse caspase-11), which in turn cleaves GSDMD and indirectly activates the NLRP3 inflammasome, amplifying inflammatory signaling. Under specific stimuli, activated caspase-3 cleaves GSDME, releasing the GSDME-NT porogenic fragment, which induces pyroptosis. The death of mouse macrophages induced by Yersinia YopJ and other factors can be…

FIGURE 3. Schematic illustrating the association of NLRP3 with various cardiovascular diseases. This figure systematically summarizes the key roles of the NLRP3 inflammasome in various cardiovascular diseases and the pathological mechanisms it mediates. Overexpression of the NLRP3 inflammasome contributes extensively to the onset and progression of diseases such as atherosclerosis, myocardial ischemia/reperfusion injury, heart failure, myocardial infarction, diabetic cardiomyopathy, and atrial fibrillation by promoting the maturation of inflammatory cytokines (such as IL-1β and IL-18) and inducing pyroptosis. Xu, Q. (2026). Schematic illustrating the association of NLRP3 with various cardiovascular diseases. Created in BioRender. https://BioRender.com/vlxum93.