Transfer and expression of the interferon gamma gene in human endothelial cells inhibits vascular smooth muscle cell growth in vitro

Alison T. Stopeck, Mahmood Vahedian, Stuart K. Williams

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Intimal hyperplasia in blood vessels is primarily caused by the migration and proliferation of vascular smooth muscle cells. Excessive intimal thickening characterizes atherosclerosis as well as bypass graft and angioplasty failures. Endothelial cell-smooth muscle cell interactions and local cytokine production are important regulators of smooth muscle cell growth. Interferon gamma (γ-IFN), a product of T lymphocytes found in atherosclerotic lesions, inhibits smooth muscle cell proliferation in vitro. To determine if local delivery of γ-IFN may be useful in the treatment or prevention of vascular proliferative diseases, we transferred the human γ- IFN gene into endothelial cells isolated from human arteries and microvessels using a retrovital vector. Biologically active γ-IFN was produced and secreted by γ-IFN transduced endothelial cells, but not by control, nontransduced cells, or cells identically transduced with E. coli beta galactosidase (β-gal). To more closely approximate the micrnenvironment of blood vessels, subconfluent smooth muscle cells were plated in coculture with control, nontransduced endothelial cells, γ-IFN transduced endothelial cells, or β-gal transduced endothelial cells. Smooth muscle cell growth was inhibited 30-7% by coculture with γ-lFN transduced endothelial cells compared to cuculture with β-gal transduced or control endothelial cells (p < 0.05). Our results suggest endothelial cells modified to produce γ-IFN may be a useful therapy in proliferative vascular diseases.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalCell transplantation
Volume6
Issue number1
DOIs
StatePublished - Jan 1 1997

Keywords

  • Endothelial cells
  • Gamma interferon
  • Gene transfer
  • Smooth muscle cells

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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