Resveratrol ameliorates endothelial dysfunction in diabetic and obese mice through sirtuin 1 and peroxisome proliferator-activated receptor δ

Publication date: Available online 29 November 2018Source: Pharmacological ResearchAuthor(s): Wai San Cheang, Wing Tak Wong, Li Wang, Chak Kwong Cheng, Chi Wai Lau, Ronald Chin Wan Ma, Aimin Xu, Nanping Wang, Yu Huang, Xiao Yu TianAbstractSirtuin 1 (SIRT1) activation reduces oxidative stress, inhibits inflammatory responses, and retards cellular senescence in endothelial cells in mouse models of diabetes. However, whether SIRT1 also plays a protective role in vascular dysfunction of diabetic and obese mice is not fully characterized. Previous work showed that peroxisome proliferator-activated receptor δ (PPARδ) is beneficial in diabetic vascular dysfunction. Whether PPARδ is involved in the beneficial effect of SIRT1 on vascular endothelial function is unknown. We used mice with overexpression of endothelial cell-specific human SIRT1 (SIRT1-Tg) and dominant-negative SIRT1 (SIRT1-mut) fed with normal chow and high fat diet to show that expression of functional SIRT1 in endothelium protects against vascular dysfunction in diet-induced obese mice. Endothelial-specific overexpression of SIRT1 improved endothelium-dependent dilation in aortas treated with risk factors including high glucose, angiotensin II, and lysophosphatidylcholine. Oral treatment with resveratrol treatment improves endothelial function in high fat diet fed wild type Ppard-wt but not in PPARδ knockout Ppard-mut mice. Experiments on isolated arteries also showed that the effect of resveratrol or SIRT1 activa...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research