Niacin protects against vascular calcification via enhanced SIRT1 and SIRT6 signaling and promoted VSMC autophagy

Chen, S.-l.; Kong, C.-H.; Wu, L.; Sun, Y.; Jiang, X.-M.; Shi, Y.; Wang, F.; Wang, D.-C.; Gu, Y.; Zhou, W.; Luo, J.; Chao, Y.

doi:10.1101/2025.01.07.631823

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bioRxiv · 10.1101/2025.01.07.631823

Niacin protects against vascular calcification via enhanced SIRT1 and SIRT6 signaling and promoted VSMC autophagy

Chen, S.-l.·Kong, C.-H.·Wu, L.·Sun, Y.·Jiang, X.-M.·Shi, Y.·Wang, F.·Wang, D.-C.·Gu, Y.·Zhou, W.·Luo, J.·Chao, Y.

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Abstract

BackgroundVascular calcification (VC) is a common pathologic state that often accompanies calcium-phosphorus metabolism disorder and chronic kidney diseases (CKDs) in aging individuals. Vascular smooth muscle cell (VSMC) has been widely acknowledged as one of the main cell types that involved in this process. Niacin, a lipid-lowering reagent, has been demonstrated to be beneficial in atherosclerotic disease. The correlation and mechanism between niacin and vascular calcification have not been reported so far. Methods and resultsRCS analysis based on large clinical databases indicated that diet that riches in niacin can protect against abdominal artery calcification (AAC). Our data showed that niacin treatment remarkably reduced VSMC osteogenic differentiation and senescence-associated markers under osteogenic stimulation. Moreover, niacin treatment alleviated CKD and vitamin D3-induced vascular calcification in C57BL/6J mice. Mechanistically, we for the first time demonstrated that niacin supplementation inhibited vascular calcification via maintaining both Sirtuin 1 (SIRT1) and Sirtuin 6 (SIRT6) levels. Moreover, we verified that niacin activated SIRT1 and SIRT6 promoted VSMC autophagy flux. ConclusionsThese findings may help to develop novel therapeutic strategies in the treatment and prevention of vascular calcification.

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Chen, S.-l., Kong, C.-H., Wu, L., Sun, Y., Jiang, X.-M., Shi, Y., Wang, F., Wang, D.-C., Gu, Y., Zhou, W., Luo, J., Chao, Y.. 2025-01-10. Niacin protects against vascular calcification via enhanced SIRT1 and SIRT6 signaling and promoted VSMC autophagy. https://doi.org/10.1101/2025.01.07.631823

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