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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 ; Ki-Chul Hwang ; Yangsoo Jang ; Onju Ham ; Soyeon Lim ; Eunmi Choi ; Heesang Song ; Min-Ji Cha ; Byeong-Wook Song ; Se-Yeon Lee 
Citation
 Cell Biology International, Vol.36(3) : 305~310, 2012 
Journal Title
 Cell Biology International 
ISSN
 1065-6995 
Issue Date
2012
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/89902
DOI
10.1042/CBI20100524
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
1. 연구논문 > 1. College of Medicine > Medical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 5. Research Institutes > Yonsei Cardiovascular Research Institute
1. 연구논문 > 5. Research Institutes > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease
Yonsei Authors
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Link
 http://onlinelibrary.wiley.com/doi/10.1042/CBI20100524/abstract
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