6533b7ddfe1ef96bd12736a7
RESEARCH PRODUCT
Adenoviral RB2/p130 gene transfer inhibits smooth muscle cell proliferation and prevents restenosis after angioplasty.
Marialuisa LavitranoAlan R. DavisAntonio GiordanoGianluigi CondorelliBruno TrimarcoShin Ichiro NumataMassimo VolpeFelicia FarinaLuigi FrattaGiorgio StassiJames M. WilsonCandace M. HowardCarmen PacilioPier Paolo Claudiosubject
NeointimaTranscriptional Activationmedicine.medical_specialtyPhysiologyadenovirus; cell cycle; gene therapy; p130; prb2; restenosisCellGenetic VectorsCell Cycle ProteinsPulmonary ArteryMuscle Smooth VascularAdenoviridaeCatheterizationPathogenesisRestenosisRecurrencemedicineAnimalsCarotid StenosisAngioplasty Balloon CoronaryGenes RetinoblastomaCells CulturedNeointimal hyperplasiaWound HealingRetinoblastoma-Like Protein p130business.industryCell growthGenetic transferCell CycleProteinsGenetic TherapyCell cyclemedicine.diseasePhosphoproteinsSurgeryE2F Transcription FactorsRatsDNA-Binding Proteinsmedicine.anatomical_structureCancer researchCardiology and Cardiovascular MedicinebusinessCarotid Artery InjuriesCarrier ProteinsTunica IntimaTranscription Factor DP1Cell DivisionRetinoblastoma-Binding Protein 1Transcription Factorsdescription
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 0 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1999-11-26 | Circulation research |