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Dominant negative insulin-like growth factor-1 receptor inhibits neointimal formation through suppression of vascular smooth muscle cell migration and proliferation, and induction of apoptosis

Authors
 Hyun-Joung Lim 1 , Hyun-Young Park, Young-Guk Ko, Sea-Hyoung Lee, Seung-Yeon Cho, Eun Jig Lee, J Larry Jameson, Yangsoo Jang 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.325(3) : 1106-1114, 2004-12 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2004-12
MeSH
Angioplasty, Balloon / adverse effects ; Animals ; Apoptosis / drug effects ; Apoptosis / genetics ; Cell Movement / drug effects ; Cell Movement / genetics ; Cell Proliferation / drug effects ; Cells, Cultured ; Coronary Restenosis / etiology ; Coronary Restenosis / genetics ; Coronary Restenosis / pathology* ; Coronary Restenosis / prevention & control* ; Gene Transfer Techniques* ; Genes, Dominant / genetics ; Genetic Therapy / methods ; Male ; Muscle, Smooth, Vascular / drug effects ; Muscle, Smooth, Vascular / physiopathology* ; Rats ; Rats, Sprague-Dawley ; Receptor, IGF Type 1 / agonists* ; Receptor, IGF Type 1 / genetics* ; Treatment Outcome ; Tunica Intima / drug effects ; Tunica Intima / growth & development ; Tunica Intima / pathology
Abstract
Blocking of the IGF-1 signaling pathway targeting the IGF-1 receptor (IGF-1R) provides a potential treatment strategy for restenosis. In this study, we have examined the effects of a dominant negative IGF-1R (IGF-1Rt) on primary rat VSMCs in vitro and on injured rat carotid artery in vivo. Ad/IGF-1Rt infection inhibited VSMC migration and proliferation, and it also induced apoptosis by inhibiting phosphorylation of Akt and phosphorylation of ERK1/2. Consistent with the anti-proliferative and apoptotic effects in vitro, the Ad/IGF-1Rt infection markedly reduced neointimal formation in carotid injury model. Ad/IGF-1Rt treated carotid arteries exhibited a suppressed proliferation index, PCNA expression, and also were stained positive for TUNEL assay. These results indicate that a dominant negative IGF-1R has the potential to reduce neointimal formation of injured rats' carotid arteries. The delivery of dominant negative IGF-1R by adenoviral or other vectors may provide a useful strategy for inhibiting restenosis after angioplasty.
Full Text
https://www.sciencedirect.com/science/article/pii/S0006291X04024234
DOI
10.1016/j.bbrc.2004.10.175
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Ko, Young Guk(고영국) ORCID logo https://orcid.org/0000-0001-7748-5788
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/178802
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