Open AccessRosiglitazone via PPAR γ‐dependent suppression of oxidative stress attenuates endothelial dysfunction in rats fed homocysteine thiolactone
Author(s) -
Yang XuHong,
Li Peng,
Yin YaLing,
Tu JiangHua,
Dai Wen,
Liu LiYing,
Wang ShuangXi
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12510
Subject(s) - apocynin , oxidative stress , endothelial dysfunction , malondialdehyde , chemistry , endocrinology , superoxide dismutase , medicine , pharmacology , nitric oxide , reactive oxygen species , nadph oxidase , biochemistry , biology
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.