Longitudinal stretch and pressure facilitate gene transfer into rabbit aortic media without endothelial denudation

M. D. Rekhter, R. D. Simari, C. Work, E. G. Nabel, D. Gordon

Research output: Contribution to journalArticle

Abstract

Smooth muscle cells (SMC) of the arterial media are a cellular source of myointimal thickening, and therefore are attractive targets for gene therapy. However, most of the medial SMCs are resistant to gene transfer unless the artery wall undergoes injury. We hypothesized that endothelium and/or extracellular connective tissue serve as mechanical barriers for virus penetration to medial SMCs, and that manipulations which increase the "porosity" of the artery can make those cells prone to gene transfer. A recombinant adenovirus vector (Ad-hpAP) encoding the reporter gene, human alkaline phosphatase (AP), was introduced into the rabbit aorta in organ culture (1-2 × 109 pfu/ml for 3 hr). Incubation with Ad-hpAP resulted in AP expression only in endothelium and adventitia. Pressurization of the vessel without endothelial denudation did not result in medial SMC infection. However, a combination of pressure (200 mm Hg) and longitudinal arterial stretch (1.5x of the original length) resulted in the infection of 10-20% of medial SMCs, 100% of endothelial cells, and 10-25% of adventitial cells. By scanning electron microscopy, gaps between endothelial cells, and increased porosity of the internal elastica were observed. Thus, stretch and pressure facilitate gene transfer into medial SMCs without denudation.

Original languageEnglish (US)
Pages (from-to)A1139
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Longitudinal stretch and pressure facilitate gene transfer into rabbit aortic media without endothelial denudation'. Together they form a unique fingerprint.

  • Cite this

    Rekhter, M. D., Simari, R. D., Work, C., Nabel, E. G., & Gordon, D. (1996). Longitudinal stretch and pressure facilitate gene transfer into rabbit aortic media without endothelial denudation. FASEB Journal, 10(6), A1139.