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Adenovirus-mediated delivery of the Gax transcription factor to rat carotid arteries inhibits smooth muscle proliferation and induces apoptosis

Gene Therapy volume 6, pages 758–763 (1999)Cite this article

Abstract

Adenovirus-mediated gene delivery in animal models of vascular injury has provided insights into the mechanisms underlying vessel wall pathologies. We have previously demonstrated that overexpression of the Gax transcription factor inhibits neointimal formation in rat and rabbit models of arterial injury. Here, we evaluate potential mechanisms for the reduction in stenotic lesion size due to Gax overexpression. At 3, 7 and 14 days after injury the Ad-Gax-infected arteries displayed a marked decrease in medial vascular smooth muscle cell number (3 days, 54% reduction P < 0.01; 7 days, 41% reduction p < 0.003; 14 days, 49% reduction p < 0.02). at 3 days after injury, pcna expression was attenuated in the ad-gax-treated vessels compared with control vessels (65% reduction p < 0.02), indicating a reduction in cellular proliferation. at 7 days and 14 days after injury ad-gax-infected arteries exhibited elevated number of tunel-positive medial vsmcs compared with control-treated arteries (7 days, 9.2-fold increase p < 0.03; 14 days, 17.2-fold increase p < 0.03), indicating an induction of apoptotic cell death. these data suggest that deregulated gax expression induces first cell cycle arrest and then apoptosis in the vascular smooth muscle cells that contribute to the neointimal layer. therefore, the efficacy of this therapeutic strategy appears to result from the ability of the gax transcriptional regulator to modulate multiple cellular responses.

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Author notes

  1. H Perlman

    Present address: Division of Arthritis, Northwestern University Medical School, 303 East Chicago, Chicago, 60611, IL, USA

Authors and Affiliations

  1. Division of Cardiovascular Research, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA, USA

    H Perlman, K Krasinski, R C Smith & K Walsh

  2. Program in Cell, Molecular and Developmental Biology, Tufts University, Sackler School of Biomedical Studies, Boston, MA, USA

    H Perlman, Z Luo & K Walsh

  3. Rhône-Poulenc Rorer Gencell, Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France

    A Le Roux, A Mahfoudi & D Branellec

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  1. H Perlman
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Perlman, H., Luo, Z., Krasinski, K. et al. Adenovirus-mediated delivery of the Gax transcription factor to rat carotid arteries inhibits smooth muscle proliferation and induces apoptosis. Gene Ther 6, 758–763 (1999). https://doi.org/10.1038/sj.gt.3300893

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  • DOI: https://doi.org/10.1038/sj.gt.3300893

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