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Exp Mol Pathol. 2010 Feb;88(1):133-7. doi: 10.1016/j.yexmp.2009.09.011. Epub 2009 Sep 28.

High glucose enhances angiotensin-II-mediated peroxisome proliferation-activated receptor-gamma inactivation in human coronary artery endothelial cells.

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  • 1Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China. baimin0628@163.com

Abstract

Activation of the renin-angiotensin system plays an important role in the pathogenesis of vascular complications of hyperglycemia. Clinical studies have demonstrated that hypoglycemic effects of peroxisome proliferation-activated receptor-gamma (PPAR-gamma) activation is potentially associated with a significant decrease of cardiovascular disease events in diabetes patients. We assessed the effect of high glucose on the angiotensin II (Ang II), which induced the inactivation of PPAR-gamma and its signal pathways in human coronary artery endothelial cells (HCAECs). The expression of angiotensin II receptor I (AT1R) protein was analyzed by Western blot and knocked down using siRNA. PPAR-gamma activation was examined using a luminometer and a Dual Luciferase Reporter Assay System. Adhesion molecule expressions of HCAECs were measured using ELISA. Both high glucose and Ang II induced a progressive increase in AT1R protein expression on the HCAECs. Troglitazone, a PPAR-gamma activator, significantly increased the transcription activity of PPAR-gamma in HCAECs in vitro. However, activation of PPAR-gamma was significantly inhibited by high glucose and Ang II stimulation. Furthermore, silencing of AT1R expression was able to inhibit the inactivation of PPAR-gamma induced by Ang II and high glucose. Meanwhile, expression of proinflammatory adhesion molecules was increased by high glucose and Ang II in HCAECs, which is blocked by troglitazone and silencing of AT1R expression. These data strongly suggest high glucose enhanced Ang-II-mediated peroxisome proliferation-activated receptor-gamma inactivation and expression of proinflammatory adhesion molecules in human coronary artery endothelial cells.

Copyright 2009 Elsevier Inc. All rights reserved.

PMID:
19796634
[PubMed - indexed for MEDLINE]
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