Resveratrol ameliorates high glucose and high-fat/sucrose diet-induced vascular hyperpermeability involving Cav-1/eNOS regulation

Vascular endothelial hyperpermeability is one of the manifestations of endothelial dysfunction. Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeabi...

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Veröffentlicht in:PloS one 2014-11, Vol.9 (11), p.e113716-e113716
Hauptverfasser: Peng, Xiao Lin, Qu, Wei, Wang, Lin Zhi, Huang, Bin Qing, Ying, Chen Jiang, Sun, Xiu Fa, Hao, Li Ping
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Qu, Wei
Wang, Lin Zhi
Huang, Bin Qing
Ying, Chen Jiang
Sun, Xiu Fa
Hao, Li Ping
description Vascular endothelial hyperpermeability is one of the manifestations of endothelial dysfunction. Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeability have not been completely clarified. The aim of present study is to investigate the effects of Res on amelioration of endothelial hyperpermeability and the role of caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) pathway. Adult male Wistar rats were treated with a normal or high-fat/sucrose diet (HFS) with or without Res for 13 weeks. HFS and in vitro treatment with high glucose increased hyperpermeability in rat aorta, heart, liver and kidney and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Application of Res reversed the changes in eNOS and Cav-1 expressions in aorta and heart of rats fed HFS and in BAECs incubated with high glucose. Res stimulated the formation of NO inhibited by high glucose in BAECs. Beta-Cyclodextrin (β-CD), caveolae inhibitor, showed the better beneficial effect than Res alone to up-regulate eNOS phosphorylative levels, while NG-Nitro-77 L-arginine methyl ester (L-NAME), eNOS inhibitor, had no effect on Cav-1 expression. Our studies suggested that HFS and in vitro treatment with high glucose caused endothelial hyperpermeability, which were ameliorated by Res at least involving Cav-1/eNOS regulation.
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Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeability have not been completely clarified. The aim of present study is to investigate the effects of Res on amelioration of endothelial hyperpermeability and the role of caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) pathway. Adult male Wistar rats were treated with a normal or high-fat/sucrose diet (HFS) with or without Res for 13 weeks. HFS and in vitro treatment with high glucose increased hyperpermeability in rat aorta, heart, liver and kidney and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Application of Res reversed the changes in eNOS and Cav-1 expressions in aorta and heart of rats fed HFS and in BAECs incubated with high glucose. Res stimulated the formation of NO inhibited by high glucose in BAECs. Beta-Cyclodextrin (β-CD), caveolae inhibitor, showed the better beneficial effect than Res alone to up-regulate eNOS phosphorylative levels, while NG-Nitro-77 L-arginine methyl ester (L-NAME), eNOS inhibitor, had no effect on Cav-1 expression. Our studies suggested that HFS and in vitro treatment with high glucose caused endothelial hyperpermeability, which were ameliorated by Res at least involving Cav-1/eNOS regulation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25419974</pmid><doi>10.1371/journal.pone.0113716</doi><oa>free_for_read</oa></addata></record>
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subjects Angiogenesis Inhibitors - pharmacology
Animals
Aorta
Arginine
Biology and Life Sciences
Blotting, Western
Capillary Permeability - drug effects
Cattle
Caveolae
Caveolin
Caveolin 1 - genetics
Caveolin 1 - metabolism
Caveolin-1
Cells, Cultured
Cyclodextrins
Diet
Diet, High-Fat
Dietary Carbohydrates
Dietary Fats - administration & dosage
Endothelial cells
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Gene Expression Regulation - drug effects
Glucose
Glucose - administration & dosage
Heart
Inhibitors
Kidneys
Kinases
Liver
Male
Medicine and Health Sciences
NG-Nitroarginine methyl ester
Nitric oxide
Nitric Oxide Synthase Type III - genetics
Nitric Oxide Synthase Type III - metabolism
Nitric-oxide synthase
Nutrition
Phosphorylation - drug effects
Polyphenols
Rats
Rats, Wistar
Resveratrol
Reverse Transcriptase Polymerase Chain Reaction
Rodents
Stilbenes - pharmacology
Sucrose
Sucrose - administration & dosage
Sugar
β-Cyclodextrin
title Resveratrol ameliorates high glucose and high-fat/sucrose diet-induced vascular hyperpermeability involving Cav-1/eNOS regulation
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