Pathobiological role of advanced glycation endproducts via mitogen-activated protein kinase dependent pathway in the diabetic vasculopathy.
10.3858/emm.2008.40.4.398
- Author:
Young Won YOON
1
;
Tae Soo KANG
;
Byoung Kwon LEE
;
Woochul CHANG
;
Ki Chul HWANG
;
Ji Hyuck RHEE
;
Pil Ki MIN
;
Bum Kee HONG
;
Se Joong RIM
;
Hyuck Moon KWON
Author Information
1. Division of Cardiology, Yong Dong Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. kwonhm@yuhs.ac
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
therosclerosis;
blood vessels;
diabetes mellitus;
glycation end products, advanced;
mitogen-activated protein kinases
- MeSH:
Animals;
Carotid Artery Diseases/metabolism/pathology;
Cell Proliferation/drug effects;
Cells, Cultured;
Diabetic Angiopathies/*etiology/metabolism/pathology;
Extracellular Signal-Regulated MAP Kinases/metabolism;
Glycosylation End Products, Advanced/adverse;
Humans;
MAP Kinase Signaling System/drug effects/*physiology;
Phosphorylation/drug effects;
RNA, Small Interfering/pharmacology;
Rats;
Rats, Sprague-Dawley;
Reactive Oxygen Species/metabolism;
Receptors, Immunologic/antagonists & inhibitors/metabolism
- From:Experimental & Molecular Medicine
2008;40(4):398-406
- CountryRepublic of Korea
- Language:English
-
Abstract:
Advanced glycation endproducts (AGEs) have been reported to play a role in neointimal formation and increase the rate of in-stent restenosis (ISR) in the diabetic coronary artery disease patients treated with stents, but the potential pathogenic mechanisms of AGEs in vascular smooth muscle cell proliferation remain unclear. We sought to determine the AGEs related pathobiological mechanism of diabetic vasculopathy. Rat aortic smooth muscle cell (RAoSMC) culture was done with different concentrations of AGEs and proliferation was assessed. Immunohistochemistry for receptor of AGEs (RAGE) was performed with human carotid atheroma. Western blotting was performed to assess the activation of MAP kinase system in the cultured RAoSMC. AGEs increased RAoSMC proliferation and were associated with increased phosphorylation of ERK and p38 kinase by time and dose dependent manner. The MAP kinase activity was decreased by RNA interference for RAGE. AGEs stimulation increased reactive oxygen species (ROS) generation in cultured RAoSMC. From this study it is concluded that AGEs played a key role in RAoSMC proliferation via MAP kinase dependent pathways. Activation of vascular smooth muscle cell (VSMC) proliferation by MAP kinase system and increased formation of ROS may be the possible mechanisms of AGEs induced diabetic vasculopathy.
