title: Rosiglitazone via PPARγ-dependent suppression of oxidative stress attenuates endothelial dysfunction in rats fed homocysteine thiolactone.
abstract: To explore whether rosiglitazone (RSG), a selective peroxisome proliferator-activated receptor γ (PPARγ) agonist, exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hrs significantly reduced cell viabilities assayed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, as well as enhanced productions of reactive oxygen species, activation of nuclear factor kappa B, and increased intercellular cell adhesion molecule-1 secretion. Pre-treatment of cells with RSG (0.001-0.1 mM), pyrollidine dithiocarbamate (PDTC, 0.1 mM) or apocynin (0.1 mM) for 1 hr reversed these effects induced by HTL. Furthermore, co-incubation with GW9662 (0.01 mM) abolished the protective effects of RSG on HTL-treated cells. In ex vivo experiments, exposure of isolated aortic rings from. rats to HTL (1 mM) for 1 hr dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced release of nitric oxide and activity of superoxide dismutase, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with RSG (0.1, 0.3, 1 mM), PDTC or apocynin normalized the disorders induced by HTL. In vivo analysis indicated that administration of RSG (20 mg/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed HTL (50 mg/kg/d) for 8 weeks. RSG improves endothelial functions in rats fed HTL, which is related to PPARγ-dependent suppression of oxidative stress.
authors: Department of Pharmacology, Pharmaceutical College, Central South University, Changsha, China.
authors: Xu-Hong
authors: XH
authors: Yang
authors: Peng
authors: P
authors: Li
authors: Ya-Ling
authors: YL
authors: Yin
authors: Jiang-Hua
authors: JH
authors: Tu
authors: Wen
authors: W
authors: Dai
authors: Li-Ying
authors: LY
authors: Liu
authors: Shuang-Xi
authors: SX
authors: Wang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006710:Homocysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D006710:Homocysteine; C007957:homocysteine thiolactone; D019255:NADPH Oxidases
keywords: endothelial dysfunction; homocysteine thiolactone; oxidative stress; rosiglitazone; vascular ageing
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