Efficient and selective adenovirus-mediated gene transfer into vascular neointima

Raul J. Guzman, Patricia Lemarchand, Ronald Crystal, Stephen E. Epstein, Toren Finkel

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Background. Previous attempts to target arterial smooth muscle cells (SMCs) for gene delivery using liposomal or retroviral methods were limited by low transfection efficiency. We therefore evaluated the efficiency of adenovirus-mediated gene delivery in cultured vascular SMCs and in an in vivo model of balloon injury-induced SMC cell proliferation. Methods and Results. We used a recombinant adenovirus, Ad.RSVβgal, which contained the β-galactosidase (β-gal) histochemical marker gene. For in vitro studies, rat aortic SMCs were incubated in media containing Ad.RSVβgal for 5 to 120 minutes. The proportion of SMCs expressing the β-gal gene product increased from 25% (5-minute exposure) to 80% (120-minute exposure). For in vivo studies, uninjured and injured rat carotid segments were incubated with 0.5 to 1.0×109 pfu Ad.RSVβgal for 45 minutes. Uninjured arteries showed adenovirus-mediated gene transfer limited to the endothelium. Injured arteries were exposed to adenovirus 0, 3, 7, or 12 days after injury. In these segments, β-gal expression was minimal with infection at 0 or 3 days after injury but marked when infection was delayed until 7 or 12 days after injury. Neointimal cells constituted the dominant target of adenovirus gene transfer, with efficiency of gene transfer ranging from 10% to >75%. Medial SMCs, whether covered or uncovered by neointimal cells, were minimally infected. Infection with a control adenovirus vector showed no β-gal staining. Conclusions. Recombinant adenovirus selectively targets neointimal cells with high-efficiency gene transfer. This suggests that adenovirus vectors should be useful in targeting cells for the delivery of genes whose products may be relevant to the treatment of restenosis.

Original languageEnglish
Pages (from-to)2838-2848
Number of pages11
JournalCirculation
Volume88
Issue number6
DOIs
Publication statusPublished - 1 Jan 1993
Externally publishedYes

Fingerprint

Neointima
Adenoviridae
Blood Vessels
Smooth Muscle Myocytes
Genes
Wounds and Injuries
Arteries
Infection
Galactosidases
Vascular Smooth Muscle
Endothelium
Transfection
Cell Proliferation
Staining and Labeling

Keywords

  • Adenovirus
  • Neointima

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Efficient and selective adenovirus-mediated gene transfer into vascular neointima. / Guzman, Raul J.; Lemarchand, Patricia; Crystal, Ronald; Epstein, Stephen E.; Finkel, Toren.

In: Circulation, Vol. 88, No. 6, 01.01.1993, p. 2838-2848.

Research output: Contribution to journalArticle

Guzman, Raul J. ; Lemarchand, Patricia ; Crystal, Ronald ; Epstein, Stephen E. ; Finkel, Toren. / Efficient and selective adenovirus-mediated gene transfer into vascular neointima. In: Circulation. 1993 ; Vol. 88, No. 6. pp. 2838-2848.
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