Curcumin Nicotinate Activates AMPK to Inhibit Aerobic Glycolysis in Vascular Endothelial Cells to Prevent Restenosis

Abstract

Abnormal proliferation of vascular smooth muscle cells (VSMCs) participates in restenosis after percutaneous coronary intervention (PCI). Curcumin, as the main active ingredient of turmeric, has been proven to inhibit the abnormal proliferation of VSMCs. This study intends to identify the mechanism whereby curcumin nicotinate (CurTn) protects against vascular restenosis. The expression of PTEN and PFKFB3 in VSMCs was detected by immunofluorescence and Western blot. Glycolysis in VSMCs was evaluated by detecting ECAR expression and MTT assays, whilst the Tandem Mass Tag (TMT)-based Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) determined expression of AMPK/PTEN/PFKFB3 in glycolysis. After treatment with CurTn, intracellular citrate and acetyl-CoA levels, and expression of triglyceride content were measured. PFKFB3 and PTEN was up-regulated in the carotid artery specimen. Overexpression of PTEN induced abnormal proliferation of VSMCs and promoted the phenotype conversion of VSMCs when increasing PFKFB3 expression. Additionally, while overexpression of AMPK did not up-regulate PFKFB3 expression, silencing of AMPK prevented the increase in PFKFB3 expression induced by PTEN. Treatment with CurTn enhanced glycolysis and increased the expression level of citrate, acetyl-CoA, and triglycerides. Importantly, PTEN overexpression increased PFKFB3 KD and PFK158 expression and alleviated CurTn-induced increase in triglyceride content. CurTn effectively delays the process of vascular restenosis through AMPK/PTEN/PFKFB3 pathway to inhibit aerobic glycolysis and VSMC proliferation.