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Combined delivery of heme oxygenase-1 gene and fibroblast growth factor-2 protein for therapeutic angiogenesis.

Abstract
Ectopic expression of heme oxygenase-1 (HO-1) in ischemic tissue protects the tissue from apoptosis and necrosis and promotes angiogenesis. However, apoptosis and necrosis will decrease HO-1 gene transfection efficacy. We hypothesized that fibroblast growth factor-2 (FGF2) would attenuate ischemic damage during the incipient period, improve HO-1 gene transfection and, in turn, enhance neovascularization. To test this hypothesis, we employed a mouse model of hindlimb ischemia and treated the mice with HO-1 gene therapy alone, FGF2 alone, or HO-1 gene therapy plus FGF2. As controls, a group of mice was left untreated. At 12h, prior to the expression of exogenously delivered HO-1, apoptosis was significantly reduced in mice treated with FGF2, either alone or in combination with HO-1 gene therapy. At 3 days, HO-1 expression was greater in mice that also received FGF2 than in mice treated with HO-1 gene therapy alone. The expression of angiogenic growth factors and angiogenesis was greater in mice treated with HO-1 gene therapy plus FGF2 than in mice treated with HO-1 gene therapy alone. These data indicate that FGF2 rescued muscle necrosis prior to the exogenous expression of HO-1 and enhanced HO-1 gene transfection in ischemic murine limbs.
AuthorsSuk H Bhang, Ju H Kim, Hee S Yang, Wan-Geun La, Tae-Jin Lee, Ah-Young Sun, Ga H Kim, Minhyung Lee, Byung-Soo Kim
JournalBiomaterials (Biomaterials) Vol. 30 Issue 31 Pg. 6247-56 (Oct 2009) ISSN: 1878-5905 [Electronic] Netherlands
PMID19682740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fibroblast Growth Factor 2
  • Heme Oxygenase-1
Topics
  • Animals
  • Apoptosis
  • Blotting, Western
  • Female
  • Fibroblast Growth Factor 2 (genetics, physiology)
  • Genetic Therapy (methods)
  • Heme Oxygenase-1 (genetics, physiology)
  • Hindlimb (pathology)
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Ischemia (pathology, therapy)
  • Mice
  • Mice, Nude
  • Necrosis
  • Neovascularization, Physiologic (genetics, physiology)
  • Random Allocation
  • Reverse Transcriptase Polymerase Chain Reaction

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