Adenoviral RB2/p130 gene transfer inhibits smooth muscle cell proliferation and prevents restenosis after angioplasty

Pier Paolo Claudio, Luigi Fratta, Felicia Farina, Candace M. Howard, Giorgio Stassi, Shin Ichiro Numata, Carmen Pacilio, Alan Davis, Marialuisa Lavitrano, Massimo Volpe, James M. Wilson, Bruno Trimarco, Antonio Giordano, Gianluigi Condorelli

Research output: Contribution to journalArticle

Abstract

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 G(o) state, 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 that RB2/p130 inhibited SMC proliferation in vitro and in vivo. We used the rat carotid artery model of restenosis to demonstrate that adenovirus-mediated localized arterial transduction of RB2/p130 at 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 that RB2/p130 could be an important target for vascular gene therapy.

Original languageEnglish
Pages (from-to)1032-1039
Number of pages8
JournalCirculation Research
Volume85
Issue number11
Publication statusPublished - Nov 26 1999

Keywords

  • Adenovirus
  • Cell cycle
  • Gene therapy
  • P130
  • PRb2
  • Restenosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Claudio, P. P., Fratta, L., Farina, F., Howard, C. M., Stassi, G., Numata, S. I., Pacilio, C., Davis, A., Lavitrano, M., Volpe, M., Wilson, J. M., Trimarco, B., Giordano, A., & Condorelli, G. (1999). Adenoviral RB2/p130 gene transfer inhibits smooth muscle cell proliferation and prevents restenosis after angioplasty. Circulation Research, 85(11), 1032-1039.