AdenoviralRB2/p130Gene Transfer Inhibits Smooth Muscle Cell Proliferation and Prevents Restenosis After Angioplasty
作者:
Pier Claudio,
Luigi Fratta,
Felicia Farina,
Candace Howard,
Giorgio Stassi,
Shin-ichiro Numata,
Carmen Pacilio,
Alan Davis,
Marialuisa Lavitrano,
Massimo Volpe,
James Wilson,
Bruno Trimarco,
Antonio Giordano,
Gianluigi Condorelli,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 1999)
卷期:
Volume 85,
issue 11
页码: 1032-1032
ISSN:0009-7330
年代: 1999
出版商: OVID
关键词: restenosis;adenovirus;cell cycle;pRb2;p130;gene therapy
数据来源: OVID
摘要:
Smooth muscle cell (SMC) proliferation that results in neointima formation is implicated in the pathogenesis of atherosclerotic plaques and accounts for the high rates of restenosis that occur after percutaneous transluminal coronary angioplasty, a widespread treatment for coronary artery disease. Endothelial lesions trigger intense proliferative signals to the SMCs of the subintima, stimulating their reentry into the cell cycle from a resting G0state, resulting in neointima formation and vascular occlusion. Cellular proliferation is negatively controlled by growth-regulatory or tumor-suppressor genes, or both, such as the retinoblastoma gene family members (RB/p105, p107, RB2/p130). In the present study, we show thatRB2/p130inhibited SMC proliferation in vitro and in vivo. We used the rat carotid artery model of restenosis to demonstrate that adenovirus-mediated localized arterial transduction ofRB2/p130at the time of angioplasty significantly reduced neointimal hyperplasia and prevented restenosis. Furthermore, the ability of pRb2/p130 to block proliferation correlated with its ability to bind and sequester the E2F family of transcription factors, which are important mediators of cell cycle progression. These results imply thatRB2/p130could be an important target for vascular gene therapy.
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