Resveratrol improves endothelial dysfunction and attenuates atherogenesis in apolipoprotein E-deficient mice

Endothelial dysfunction is an early and central feature of atherosclerosis. Dietary resveratrol (RSV), a class of flavonoid compounds, have been demonstrated to exert several beneficial effects on human body. In this study, we investigated the protective effects of RSV on high fat diet-induced endot...

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Bibliographic Details
Published in:The Journal of nutritional biochemistry 2019-05, Vol.67, p.63-71
Main Authors: Li, Jinghua, Zhong, Zhenwei, Yuan, Jiru, Chen, Xiaohang, Huang, Ziyang, Wu, Zeyu
Format: Article
Language:English
Subjects:
Atherosclerosis
CREB
eNOS
PKA
Resveratrol
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Summary:Endothelial dysfunction is an early and central feature of atherosclerosis. Dietary resveratrol (RSV), a class of flavonoid compounds, have been demonstrated to exert several beneficial effects on human body. In this study, we investigated the protective effects of RSV on high fat diet-induced endothelial dysfunction. Human aortic endothelial cells (HAECs) were treated with RSV to evaluate the gene expression of the endothelial nitric oxide synthase (eNOS). Apolipoprotein E (apoE−/−) mice were fed a high-fat, high-cholesterol diet (HCD) or HCD supplemented with RSV for 8 weeks. Treatment of cultured HAECs with RSV dose-dependently upregulated the eNOS expression as assessed by quantitative RT-PCR and Western blot, respectively. In addition, RSV increased the promoter activity of the human eNOS gene, as determined by luciferase assays of the eNOS promoter gene. The cAMP-response element binding protein (CREB) was identified as the target transcription factor involved in the RSV mediated upregulation of eNOS expression. RSV increased phosphorylation of CREB through protein kinase A (PKA) activation, which induced a CREB-mediated upregulation of eNOS transcription. Consequently, RSV treatment significantly reversed the deleterious effects of oxidized LDL (oxLDL)-induced oxidative stress in HAECs. In vivo, treatment with RSV improves endothelial dysfunction and attenuates atherosclerotic plaque formation in apoE−/− mice through PKA-CREB-dependent pathway. Our findings demonstrate that RSV has an effect of activating eNOS expression, contributing to the prevention of dyslipidemia-induced endothelial dysfunction and atherosclerosis.
ISSN:0955-2863
1873-4847
DOI:10.1016/j.jnutbio.2019.01.022