Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart

Jorge Safi, Anthony F. DiPaula, Teresa Riccioni, Jan Kajstura, Giuseppe Ambrosio, Lewis C. Becker, Piero Anversa, Maurizio C. Capogrossi

Research output: Contribution to journalArticle

Abstract

Most patients with severe coronary artery disease have normal baseline myocardial blood flow. Therefore, interventions aimed at inducing therapeutic angiogenesis in these patients should cause new blood vessel growth in the heart in the absence of chronic ischemia. It was examined whether adenovirus- mediated gene transfer of recombinant, secreted acidic fibroblast growth factor (sp+aFGF1-154), next to a major epicardial artery, may induce neovascularization and reduce the risk region for myocardial infarction upon coronary ligation near the injection site. Fifteen days prior to coronary artery occlusion, rabbits were treated with intramyocardial injections of AdCMV.sp+aFGF1-154, the control vector AdCMV.NLSβgal (1 x 109 plaque- forming units), or saline. Messenger RNA transcripts for aFGF1-154 were present up to 12 days after injection in the tissues exposed to AdCMV.aFGF1-154. Following coronary artery occlusion rabbits treated with AdCMV.sp+aFGF1-154 showed a 50% reduction of the risk region for myocardial infarction (P <0.01 vs control). Histologic analysis showed a twofold increase in length density of intramural coronary arterioles (P <0.01 vs control) and a 17% increase in length density of the capillary network (P <0.001) in the myocardium exposed to AdCMV.sp+aFGF1-154. Thus, gene therapy with AdCMV.sp+aFGF1-154 can induce angiogenesis in the absence of chronic ischemia. The newly formed collateral blood vessels provide an anatomical basis for the reduction in the risk region for myocardial infarction upon subsequent occlusion of the coronary artery in proximity of the site where angiogenesis was induced.

Original languageEnglish
Pages (from-to)238-249
Number of pages12
JournalMicrovascular Research
Volume58
Issue number3
DOIs
Publication statusPublished - Nov 1999

Fingerprint

Gene transfer
Fibroblast Growth Factor 1
Adenoviridae
Coronary Vessels
Coronary Occlusion
Myocardial Infarction
Blood vessels
Risk Reduction Behavior
Rabbits
Injections
Blood Vessels
Ischemia
Genes
Gene therapy
Arterioles
Genetic Therapy
Ligation
Coronary Artery Disease
Myocardium
Blood

Keywords

  • Adenovirus
  • aFGF
  • Angiogenesis
  • Collateral circulation
  • Gene therapy

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine

Cite this

Safi, J., DiPaula, A. F., Riccioni, T., Kajstura, J., Ambrosio, G., Becker, L. C., ... Capogrossi, M. C. (1999). Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart. Microvascular Research, 58(3), 238-249. https://doi.org/10.1006/mvre.1999.2165

Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart. / Safi, Jorge; DiPaula, Anthony F.; Riccioni, Teresa; Kajstura, Jan; Ambrosio, Giuseppe; Becker, Lewis C.; Anversa, Piero; Capogrossi, Maurizio C.

In: Microvascular Research, Vol. 58, No. 3, 11.1999, p. 238-249.

Research output: Contribution to journalArticle

Safi, J, DiPaula, AF, Riccioni, T, Kajstura, J, Ambrosio, G, Becker, LC, Anversa, P & Capogrossi, MC 1999, 'Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart', Microvascular Research, vol. 58, no. 3, pp. 238-249. https://doi.org/10.1006/mvre.1999.2165
Safi, Jorge ; DiPaula, Anthony F. ; Riccioni, Teresa ; Kajstura, Jan ; Ambrosio, Giuseppe ; Becker, Lewis C. ; Anversa, Piero ; Capogrossi, Maurizio C. / Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart. In: Microvascular Research. 1999 ; Vol. 58, No. 3. pp. 238-249.
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