Niacin inhibits vascular calcification via modulating of SIRT1/SIRT6 signaling pathway

Vascular calcification (VC) is a common pathological state that often accompanies calcium-phosphorus metabolism disorder and chronic kidney diseases (CKDs). Vascular smooth muscle cell (VSMC) has been widely acknowledged as one of the main cell types involved in this process. Niacin, a lipid-lowering reagent, has been demonstrated to be beneficial in atherosclerotic disease, but its role in vascular calcification remains unexplored. Restricted cubic spline (RCS) analysis of clinical datasets revealed an inverse correlation between dietary niacin intake and abdominal aortic calcification (AAC). Our data showed that niacin treatment remarkably reduced VSMC osteogenic differentiation. Moreover, niacin treatment alleviated CKD and vitamin D₃-induced vascular calcification in C57BL/6J mice. Mechanistically, we for the first time demonstrated that niacin inhibited vascular calcification via maintaining both Sirtuin 1 (SIRT1) and Sirtuin 6 (SIRT6) levels. Further, we verified that niacin increased SIRT1 and SIRT6-mediated autophagy flux in VSMC. Our findings reveal that niacin exerts anti-calcification effect via maintaining both SIRT1 and SIRT6, providing novel therapeutic strategies in the treatment of vascular calcification.