In vivo angiogenesis induced by recombinant adenovirus vectors coding either for secreted or nonsecreted forms of acidic fibroblast growth factor. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cells, Cultured
  • Humans
  • Mice
  • Mice, Inbred C57BL

MeSH Major

  • Adenoviridae
  • Fibroblast Growth Factor 1
  • Gene Transfer Techniques
  • Genetic Vectors
  • Neovascularization, Physiologic

abstract

  • In vivo gene transfer of angiogenic growth factors represents a potential approach to the treatment of ischemic diseases. The present study examined the in vitro and in vivo effects of two replication-deficient recombinant adenovirus (Ad) vectors coding for human acidic fibroblast growth factor (aFGF1-154). One vector codes for the nonsecreted form of the peptide (AdCMV.aFGF1-154), and the other vector codes for a recombinant, secreted form (AdCMV.sp+aFGF1-154). AdCMV.NLS beta gal, an adenovirus vector coding for beta-galactosidase (beta-Gal), was used as a control. Assessment of proliferation of starved human umbilical vein endothelial cells infected with AdCMV.aFGF1-154 and AdCMV.sp+aFGF1-154 (20 pfu/cell) showed approximately 6- and 10-fold increase in cell number over control, respectively. Infection with AdCMV.sp+aFGF1-154 and with AdCMV.aFGF1-154 enhanced endothelial cell differentiation into capillary-like structures in vitro. However, this effect was significantly more pronounced with AdCMV.sp+aFGF1-154 than with AdCMV.aFGF1-154. Angiogenesis in vivo was assessed by injecting subcutaneously into mice 750 microliters of reconstituted basement membrane proteins (Matrigel) and the Ad vectors (2 x 10(8) pfu). After 14 days, there was histologic evidence of neovascularization in the animal's tissue surrounding the Matrigel plugs with AdCMV.aFGF1-154 and AdCMV.sp+aFGF1-154. Further, the hemoglobin content of the Matrigel plugs with AdCMV.aFGF1-154 and with AdCMV.sp+aFGF1-154 was, respectively, 2.3- and 2.6-fold higher than with AdCMV.NLS beta gal. Together, these observations support the concept that adenovirus vectors coding for various forms of acidic FGF1-154 may be used to induce angiogenesis in vivo and may provide a new therapeutic approach to ischemic diseases.

publication date

  • November 1995

has subject area

  • Adenoviridae
  • Animals
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cells, Cultured
  • Fibroblast Growth Factor 1
  • Gene Transfer Techniques
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1089/hum.1995.6.11-1457

PubMed ID

  • 8573618

Additional Document Info

start page

  • 1457

end page

  • 1465

volume

  • 6

number

  • 11