High glucose enhances angiotensin-II-mediated peroxisome proliferation-activated receptor-γ inactivation in human coronary artery endothelial cells
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- 作者：Qing Min ; Yu-Ting Bai ; Guanghong Jia ; Jiliang Wu ; Ji-Zhou Xiang
- 关键词：Vascular endothelial cells ; Angiotensin II ; High glycemia ; Atherosclerosis ; Peroxisome Proliferation-activated receptor-γ ; Adhesion molecules
- 刊名：Experimental and Molecular Pathology
- 出版年：2010
- 出版时间：February 2010
- 年：2010
- 卷：88
- 期：1
- 页码：133-137
- 全文大小：394 K
文摘
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-γ (PPAR-γ) 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-γ 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-γ 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-γ activator, significantly increased the transcription activity of PPAR-γ in HCAECs in vitro. However, activation of PPAR-γ was significantly inhibited by high glucose and Ang II stimulation. Furthermore, silencing of AT1R expression was able to inhibit the inactivation of PPAR-γ 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-γ inactivation and expression of proinflammatory adhesion molecules in human coronary artery endothelial cells.