Resveratrol Nanoparticles Inhibit Endothelial Dysfunction in Abdominal Aortic Aneurysm by Preventing eNOS Uncoupling Through Sirtuin 1 Pathway

Abstract

Abdominal aortic aneurysm (AAA) is a pathological condition of chronic dilation of the aorta. This study investigated the mechanism underlying the inhibitory effect of resveratrol nanoparticles on AAA endothelial dysfunction. Mice in the control group received normal saline ( n = 18) while those in the model group ( n = 18) were implanted with Alzet micropumps to induce AAA. After modeling, the endothelial cells of abdominal aortic tissue were collected and treated with resveratrol nanoparticles and resveratrol nanoparticles plus sirtuin 1 (SIRT1) (resveratrol nanoparticles+SIRT1 group). CCK-8 method detected proliferation ability of abdominal aortic endothelial cells, flow cytometry assessed cell apoptosis, and transwell method measured the migration ability along with analysis of SIRT1 level, eNOS and NO content. The proliferation ability of endothelial cells was significantly decreased in resveratrol nanoparticles group (0.41±0.04, 0.60±0.05, 0.69±0.04) and resveratrol+SIRT1 group (0.37±0.05, 0.49±0.04, 0.57±0.04), with lower proliferation in resveratrol+SIRT1 group ( P <0.05). Treatment resulted in enhancement of endothelial cell apoptosis and decreased migration ability ( P <0.05), as the effect of combined treatment was more significant. Moreover, resveratrol nanoparticles (0.44±0.02, 0.34±0.05) or resveratrol nanoparticles plus SIRT1 (0.50±0.01, 0.44±0.03) increased SIRT1 level ( P <0.05), eNOS activity and NO secretion ( P <0.05) in the resveratrol+SIRT1 group. Resveratrol nanoparticles can reduce endothelial cell proliferation and migration and induce apoptosis when increasing SIRT1 expression.