The roles of NLRP3 inflammasome in diabetic cardiomyopathy and potential targeted therapeutics

Diabetic cardiomyopathy (DbCM) is a chronic inflammatory condition driven by metabolic dysregulation. The NLRP3 inflammasome, a pivotal hub of innate immunity, integrates metabolic stress signals such as hyperglycemia and lipotoxicity to activate inflammatory cascades, playing a central role in DbCM pathogenesis. This review outlines the molecular mechanisms and spatiotemporal regulation of NLRP3 in DbCM, detailing its involvement in inflammation, oxidative stress, pyroptosis, fibroblast transdifferentiation, macrophage polarization, and endothelial injury. We further propose a multidimensional strategy targeting NLRP3 to overcome "metabolic memory" and "inflammatory residual effect" to achieve sustained remission of DbCM, including: i) screening natural bioactive compounds; ii) developing small-molecule inhibitors; and iii) precisely modulating NLRP3 post-translational modifications epigenetically. This review evaluates the clinical potential and challenges of these strategies. Comprehensive targeting of the NLRP3 network may break the "metabolism–inflammation" vicious cycle in DbCM, offering new directions for therapies with dual anti-inflammatory and metabolic benefits.