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Pathobiological role of advanced glycation endproducts via mitogen-activated protein kinase dependent pathway in the diabetic vasculopathy.

Authors
 Young Won Yoon  ;  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 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.40(4) : 398-406, 2008 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2008
MeSH
Animals ; Carotid Artery Diseases/metabolism ; Carotid Artery Diseases/pathology ; Cell Proliferation/drug effects ; Cells, Cultured ; Diabetic Angiopathies/etiology* ; Diabetic Angiopathies/metabolism ; Diabetic Angiopathies/pathology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Glycation End Products, Advanced/adverse effects ; Glycation End Products, Advanced/metabolism ; Glycation End Products, Advanced/pharmacology ; Glycation End Products, Advanced/physiology* ; Humans ; MAP Kinase Signaling System/drug effects ; MAP Kinase Signaling System/physiology* ; Phosphorylation/drug effects ; RNA, Small Interfering/pharmacology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic/antagonists & inhibitors ; Receptors, Immunologic/metabolism
Keywords
atherosclerosis ; blood vessels ; diabetes mellitus ; glycation end products, advanced ; mitogen-activated protein kinases
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.
Files in This Item:
T200800269.pdf Download
DOI
10.3858/emm.2008.40.4.398
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kang, Tae Soo(강태수)
Kwon, Hyuck Moon(권혁문) ORCID logo https://orcid.org/0000-0001-9901-5015
Min, Pil Ki(민필기) ORCID logo https://orcid.org/0000-0001-7033-7651
Yoon, Young Won(윤영원) ORCID logo https://orcid.org/0000-0002-0907-0350
Lee, Byoung Kwon(이병권) ORCID logo https://orcid.org/0000-0001-9259-2776
Rhee, Ji Hyuk(이지혁)
Rim, Se Joong(임세중) ORCID logo https://orcid.org/0000-0002-7631-5581
Chang, Woo Chul(장우철)
Hong, Bum Kee(홍범기) ORCID logo https://orcid.org/0000-0002-6456-0184
Hwang, Ki Chul(황기철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106400
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