Vascular endothelial growth factor-B induces myocardium-specific angiogenesis and arteriogenesis via vascular endothelial growth factor receptor-1- and neuropilin receptor-1-dependent mechanisms

Circulation. 2009 Feb 17;119(6):845-56. doi: 10.1161/CIRCULATIONAHA.108.816454. Epub 2009 Feb 2.


Background: New revascularization therapies are urgently needed for patients with severe coronary heart disease who lack conventional treatment options.

Methods and results: We describe a new proangiogenic approach for these no-option patients using adenoviral (Ad) intramyocardial vascular endothelial growth factor (VEGF)-B186 gene transfer, which induces myocardium-specific angiogenesis and arteriogenesis in pigs and rabbits. After acute infarction, AdVEGF-B186 increased blood vessel area, perfusion, ejection fraction, and collateral artery formation and induced changes toward an ischemia-resistant myocardial phenotype. Soluble VEGF receptor-1 and soluble neuropilin receptor-1 reduced the effects of AdVEGF-B186, whereas neither soluble VEGF receptor-2 nor inhibition of nitric oxide production had this result. The effects of AdVEGF-B186 involved activation of neuropilin receptor-1, which is highly expressed in the myocardium, via recruitment of G-protein-alpha interacting protein, terminus C (GIPC) and upregulation of G-protein-alpha interacting protein. AdVEGF-B186 also induced an antiapoptotic gene expression profile in cardiomyocytes and had metabolic effects by inducing expression of fatty acid transport protein-4 and lipid and glycogen accumulation in the myocardium.

Conclusions: VEGF-B186 displayed strikingly distinct effects compared with other VEGFs. These effects may be mediated at least in part via a G-protein signaling pathway. Tissue-specificity, high efficiency in ischemic myocardium, and induction of arteriogenesis and antiapoptotic and metabolic effects make AdVEGF-B186 a promising candidate for the treatment of myocardial ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / drug effects*
  • Arteries / growth & development
  • Genetic Therapy / methods
  • Genetic Vectors
  • Myocardial Infarction / therapy
  • Myocardial Ischemia / therapy*
  • Myocardial Reperfusion Injury / prevention & control
  • Neovascularization, Physiologic / drug effects*
  • Neuropilin-1 / metabolism*
  • Organ Specificity
  • Rabbits
  • Swine
  • Vascular Endothelial Growth Factor B / administration & dosage*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*


  • Vascular Endothelial Growth Factor B
  • Neuropilin-1
  • Vascular Endothelial Growth Factor Receptor-1