Expression of vascular endothelial growth factor from a defective herpes simplex virus type 1 amplicon vector induces angiogenesis in mice

Enrique A Mesri, H. J. Federoff, M. Brownlee

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) is a secreted endothelial cell- specific angiogenic growth factor. VEGF gene transfer strategies to stimulate focal angiogenesis could be used to ameliorate myocardial ischemia. To induce angiogenesis in vivo, we have constructed a replication-defective herpes simplex virus type 1 (HSV-1) amplicon vector that places the human VEGF-165 cDNA under the transcriptional control of the HSV immediate-early 4/5 promoter (HSVhvegf). Transduction of NIH 3T3 fibroblasts with HSVhvegf resulted in the secretion of high levels of biologically active VEGF, as assayed by microvascular endothelial mitogenesis. By use of an ex vivo protocol, BLK-CL4 fibroblasts were transduced with HSVhvegf or control HSVlac virus (expressing Escherichia coli β-galactosidase), resuspended in basement membrane extract (matrigel), and coinjected subcutaneously into syngeneic C57BL/6 mice. One week later, the matrigel plugs with HSVhvegf showed a strong angiogenic response, in contrast to the plugs with HSVlac-transduced fibroblasts. These data indicate that transduction with HSVhvegf virus can induce an angiogenic response in vivo and suggest that this is a viable gene therapy approach for tissue ischemia.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalCirculation Research
Volume76
Issue number2
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Defective Viruses
Human Herpesvirus 1
Vascular Endothelial Growth Factor A
Fibroblasts
Galactosidases
Viruses
Angiogenesis Inducing Agents
Inbred C57BL Mouse
Basement Membrane
Genetic Therapy
Myocardial Ischemia
Intercellular Signaling Peptides and Proteins
Ischemia
Endothelial Cells
Complementary DNA
Escherichia coli
Genes
human VEGFA protein
matrigel

Keywords

  • DNA virus
  • endothelium
  • gene therapy
  • lymphokines
  • neovascularization

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Expression of vascular endothelial growth factor from a defective herpes simplex virus type 1 amplicon vector induces angiogenesis in mice. / Mesri, Enrique A; Federoff, H. J.; Brownlee, M.

In: Circulation Research, Vol. 76, No. 2, 01.01.1995, p. 161-167.

Research output: Contribution to journalArticle

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