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

 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 
 Experimental and Molecular Medicine, Vol.40(4) : 398-406, 2008 
Journal Title
 Experimental and Molecular Medicine 
Issue Date
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.
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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
강태수(Kang, Tae Soo)
권혁문(Kwon, Hyuck Moon) ORCID logo https://orcid.org/0000-0001-9901-5015
민필기(Min, Pil Ki) ORCID logo https://orcid.org/0000-0001-7033-7651
윤영원(Yoon, Young Won) ORCID logo https://orcid.org/0000-0002-0907-0350
이병권(Lee, Byoung Kwon) ORCID logo https://orcid.org/0000-0001-9259-2776
이지혁(Rhee, Ji Hyuk)
임세중(Rim, Se Joong) ORCID logo https://orcid.org/0000-0002-7631-5581
장우철(Chang, Woo Chul)
홍범기(Hong, Bum Kee) ORCID logo https://orcid.org/0000-0002-6456-0184
황기철(Hwang, Ki Chul)
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