High glucose enhances angiotensin-II-mediated peroxisome proliferation-activated receptor-gamma inactivation in human coronary artery endothelial cells.
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.
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China. baimin0628@163.com
Qing
Q
Min
Yu-Ting
YT
Bai
Guanghong
G
Jia
Jiliang
J
Wu
Ji-Zhou
JZ
Xiang
D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020868:Gene Silencing; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D015854:Up-Regulation / Q000187:drug effects
C544065:AGTR1 protein, human; D015815:Cell Adhesion Molecules; D002839:Chromans; D047495:PPAR gamma; D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1; D045162:Thiazolidinediones; D000804:Angiotensin II; D000077288:Troglitazone; D005947:Glucose