Cytostatic gene therapy for vascular proliferative disorders with a constitutively active form of the retinoblastoma gene product

Mark W. Chang, Eliav Barr, Jonathan Seltzer, Yue Qin Jiang, Gary J. Nabel, Elizabeth G. Nabel, Michael S. Parmacek, Jeffrey M. Leiden

Research output: Contribution to journalArticlepeer-review

Abstract

Vascular smooth muscle cell (SMC) proliferation in response to injury is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis after balloon angioplasty. The retinoblastoma gene product (Rb) is present in the unphosphorylated and active form in quiescent primary arterial SMCs, but is rapidly inactivated by phosphorylation in response to growth factor stimulation in vitro. A replication defective adenovirus encoding a nonphosphorylatable, constitutively active form of Rb was constructed. Infection of cultured primary rat aortic SMCs with this virus inhibited growth factor-stimulated cell proliferation in vitro. Localized arterial infection with the virus at the time of balloon angioplasty significantly reduced SMC proliferation and neointima formation in both the rat carotid and porcine femoral artery models of restenosis. These results demonstrate the role of Rb in regulating vascular SMC proliferation and suggest a gene therapy approach for vascular proliferative disorders associated with arterial injury.

Original languageEnglish (US)
Pages (from-to)518-522
Number of pages5
JournalScience
Volume267
Issue number5197
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • General

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