Resveratrol attenuates atherosclerotic endothelial injury through the Pin1/Notch1 pathway

Abstract

The present study investigates whether resveratrol could modulate the endothelial dysfunction of atherosclerosis via the Pin1/Notch1 signaling pathway. To assess the vascular endothelial cell (VECs) injury in mice, the levels of serum soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), soluble thrombomodulin (sTM), and von Willebrand factor (vWF) were measured. Expressions of Pin1 and Notch1 intracellular domain (NICD1), both mRNA and protein, were also measured. Human umbilical vein endothelial cells (HUVECs) treated with 100 μg/mL oxidized low-density lipoprotein (ox-LDL) were incubated with resveratrol at doses from 10 μM to 40 μM. Cell function was evaluated by measuring apoptosis, cell viability, lipid accumulation, and adherent human myeloid leukemia mononuclear (THP-1) cells. Resveratrol intervention in AS mice decreased the expression of serum sVCAM-1, sICAM-1, sE-selectin, sTM, and vWF and dose-dependently down-regulated Pin1 and NICD1 mRNA and protein expression in endothelial cells. Resveratrol intervention reversed ox-LDL-induced cell dysfunction by increasing viability and decreasing apoptosis, lipid accumulation, and the adhesion of THP-1 cells. These beneficial effects were reversed by the overexpression of Pin1. Resveratrol regulates endothelial cell injury of atherosclerosis by inhibiting the Pin1/Notch1 signaling pathway, suggesting novel therapeutic targets for atherosclerosis treatment.