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Anti-proliferative effect of rosiglitazone on angiotensin II-induced vascular smooth muscle cell proliferation is mediated by the mTOR pathway

Authors
 Jung-Sun Kim  ;  Il-Kwon Kim  ;  Se-Yeon Lee  ;  Byeong-Wook Song  ;  Min-Ji Cha  ;  Heesang Song  ;  Eunmi Choi  ;  Soyeon Lim  ;  Onju Ham  ;  Yangsoo Jang  ;  Ki-Chul Hwang 
Citation
 Cell Biology International, Vol.36(3) : 305-310, 2012 
Journal Title
 Cell Biology International 
ISSN
 1065-6995 
Issue Date
2012
MeSH
Angiotensin II/metabolism* ; Animals ; Cell Proliferation*/drug effects ; Muscle, Smooth, Vascular/cytology* ; Muscle, Smooth, Vascular/metabolism ; Rats ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/metabolism* ; Thiazolidinediones/pharmacology*
Keywords
angiotensin II ; mammalian target of rapamycin (mTOR) ; proliferation ; rosiglitazone ; smooth muscle cell
Abstract
VSMC (vascular smooth muscle cell) proliferation contributes significantly to intimal thickening in atherosclerosis, restenosis and venous bypass graft diseases. Ang II (angiotensin II) has been implicated in VSMC proliferation though the activation of multiple growth-promoting signals. Although TZDs (thiazolidinediones) can inhibit VSMC proliferation and reduce Ang II-induced fibrosis, the mechanism underlying the inhibition of VSMC proliferation and fibrosis needs elucidation. We have used primary cultured rat aortic VSMCs and specific antibodies to investigate the inhibitory mechanism of rosiglitazone on Ang II-induced VSMC proliferation. Rosiglitazone treatment significantly inhibited Ang II-induced rat aortic VSMC proliferation in a dose-dependent manner. Western blot analysis showed that rosiglitazone significantly lowered phosphorylated ERK1/2 (extracellular-signal-regulated kinase 1/2), Akt (also known as protein kinase B), mTOR (mammalian target of rapamycin), p70S6K (70 kDa S6 kinase) and 4EBP1 (eukaryotic initiation factor 4E-binding protein) levels in Ang II-treated VSMCs. In addition, PPAR-γ (peroxisome-proliferator-activated receptor γ) mRNA increased significantly and CTGF (connective tissue growth factor), Fn (fibronectin) and Col III (collagen III) levels decreased significantly. The results demonstrate that the rosiglitazone directly inhibits the pro-atherosclerotic effect of Ang II on rat aortic VSMCs. It also attenuates Ang II-induced ECM (extracellular matrix) molecules and CTGF production in rat aortic VSMCs, reducing fibrosis. Importantly, PPAR-γ activation mediates these effects, in part, through the mTOR-p70S6K and -4EBP1 system.
Full Text
http://onlinelibrary.wiley.com/doi/10.1042/CBI20100524/abstract
DOI
22050182
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
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) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Cardiovascular Research Institute (심혈관연구소) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
Yonsei Authors
Kim, Il Kwon(김일권)
Kim, Jung Sun(김중선) ORCID logo https://orcid.org/0000-0003-2263-3274
Song, Byeong Wook(송병욱)
Lee, Se Yeon(이세연)
Lim, So Yeon(임소연)
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Cha, Min Ji(차민지)
Choi, Eun Mi(최은미)
Ham, On Ju(함온주)
Hwang, Ki Chul(황기철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89902
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