Vericiguat improves CKD-related vascular calcification through the NO/cGMP/PKG pathway

Chronic kidney disease (CKD) is a condition characterized by progressive loss of kidney function. Vascular calcification is not only a common late-stage complication of CKD but also serves as an independent predictor of cardiovascular events and mortality in CKD patients. This study investigates the mechanism by which vericiguat (VER), a soluble guanylyl cyclase (sGC) sensitizer, attenuates CKD-associated vascular calcification. The hypothesis that vericiguat alleviates the decrease of sGC activity mediated by calcium and phosphorus metabolism was verified in both in vitro and in vivo experimental models. The calcium levels were increased in the aorta of CKD rats and VSMCs in vitro, and the expression of osteogenic differentiation-related markers, eNOS and PKG was upregulated. Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were downregulated, while VER significantly improved calcification by activating the NO/cGMP/PKG pathway. Meanwhile, L-NAME antagonized the positive effects of VER in either CKD rats or calcified VSMCs.