期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 53, 期 2, 页码 268-276出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2012.05.008
关键词
Sex hormones; Women; Vasculature; Inflammation; Atherosclerosis
资金
- BONFOR of the University Hospital of Bonn [O-109.0028, O-109.0033]
The exact mechanism of estrogen in cardiovascular disease is not fully understood. As estrogen receptors (ERs), the peroxisome-proliferator-activated-receptor-gamma (PPAR gamma) belongs to the family of ligand activated nuclear receptors regulating atheroprotective genes. The aim of this project was to investigate whether vascular effects of estrogen are mediated via PPAR gamma-regulation in the vascular compartment. Estrogen deficient ovariectomized wildtype-mice (OVX) displayed significant reduction of PPAR gamma-expression in aortic tissue compared to wildtype-mice with intact ovarian function (Sham). Hormone replacement with subdermal 17 beta-estradiol pellets significantly increased vascular PPAR gamma-expression in ovariectomized female wildtype-mice (OVX/E2). Analogous to wildtype-mice, estrogen-deficient OVX ApoE(-/-)-mice had low vascular PPAR-expression associated with ROS generation, endothelial dysfunction and a therogenesis. Estrogen replacement (OVX/E2) rescued vascular PPAR gamma-expression, reduced ROS generation, monocyte recruitment, atherosclerotic lesion formation and improved endothelial function. Inhibition of PPAR gamma by GW9662, a specific PPAR gamma-antagonist reduced 17 beta-estradiol mediated vascular effects (OVX/E2 + GW9662). Finally, despite estrogen deficiency treatment with pioglitazone (OVX + pioglitazone), a selective PPAR gamma-agonist, compensates deterioration of vascular morphology and function. 17 beta-estradiol regulates vascular PPAR gamma-expression in wildtype- and ApoE(-/-)-mice. The presented data demonstrate the fundamental relevance of PPAR gamma as downstream target of 17 beta-estradiol-related anti-inflammatory and atheroprotective effects within the vascular wall independent of its cardiovascular risk factor modifications. (C) 2012 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据