Sodium-glucose cotransporter 2 inhibitor canagliflozin alleviates vascular calcification through suppression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome.

This article investigates the effect of canagliflozin (CANA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor approved for type 2 diabetes treatment, on vascular calcification (VC), a pathological process common in chronic kidney disease (CKD), diabetes, and atherosclerosis. Using in vitro, ex vivo, and in vivo models—including CKD rats and vitamin D3-overloaded mice—the study demonstrates that CANA reduces VC by inhibiting osteogenic differentiation of vascular smooth muscle cells (VSMCs) and downregulating the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signaling pathway. Pharmacological inhibition or genetic knockdown of NLRP3 similarly attenuated VSMC calcification, while activation of NLRP3 exacerbated it, effects that CANA counteracted. These findings suggest that CANA's protective role against VC operates independently of its glucose-lowering effects and highlight the NLRP3 inflammasome as a potential therapeutic target for VC.