Nicotinamide promotes lipophagy and cholesterol efflux through the SIRT1-LXRα deacetylation-ABCA1 pathway in vascular smooth muscle cells

作者：Sung JY, Choi PR, Kim SG, Choi HC · 发表于：Biochemical and biophysical research communications · 年份：2026 · DOI：10.1016/j.bbrc.2026.154439 · 研究领域：Atherosclerosis、Lipophagy、Nicotinamide、SIRT1、Vascular smooth muscle cells

Atherosclerosis is characterized by the abnormal accumulation of lipids within vascular smooth muscle cells (VSMCs), which contributes to foam cell formation and plaque development. Although oxidized low-density lipoprotein (oxLDL) promotes intracellular lipid deposition, the precise mechanisms regulating cholesterol homeostasis in VSMCs remain unclear. This study investigated the therapeutic potential of nicotinamide (NAM) and the molecular mechanisms underlying oxLDL-induced lipid accumulation in VSMCs. NAM treatment significantly increased SIRT1 expression and concomitantly reduced adipose differentiation-related protein levels and lipid droplet accumulation in a concentration-dependent manner. Mechanistically, co-immunoprecipitation analyses revealed that NAM improved SIRT1-mediated deacetylation of liver X receptor alpha (LXRα). LXRα deacetylation was associated with increased ABCA1 expression, resulting in improved cholesterol efflux and reduced intracellular cholesterol accumulation. Remarkably, the effects of NAM on ABCA1 expression and lipid clearance were comparable to those of the synthetic LXRα agonist T0901317. Pharmacological inhibition of SIRT1 with EX527 abolished NAM-induced LXRα deacetylation and ABCA1 upregulation, restoring lipid accumulation and confirming the SIRT1 dependency of this pathway. Moreover, LXRα inhibition with GSK2033 or autophagic flux blockade with bafilomycin A1 impaired NAM-induced lipophagy, as evidenced by increased p62 and LC3 II accu...