Vascular endothelial growth factor-B acts as a coronary growth factor in transgenic rats without inducing angiogenesis, vascular leak, or inflammation

Circulation. 2010 Oct 26;122(17):1725-33. doi: 10.1161/CIRCULATIONAHA.110.957332. Epub 2010 Oct 11.


Background: Vascular endothelial growth factor-B (VEGF-B) binds to VEGF receptor-1 and neuropilin-1 and is abundantly expressed in the heart, skeletal muscle, and brown fat. The biological function of VEGF-B is incompletely understood.

Methods and results: Unlike placenta growth factor, which binds to the same receptors, adeno-associated viral delivery of VEGF-B to mouse skeletal or heart muscle induced very little angiogenesis, vascular permeability, or inflammation. As previously reported for the VEGF-B(167) isoform, transgenic mice and rats expressing both isoforms of VEGF-B in the myocardium developed cardiac hypertrophy yet maintained systolic function. Deletion of the VEGF receptor-1 tyrosine kinase domain or the arterial endothelial Bmx tyrosine kinase inhibited hypertrophy, whereas loss of VEGF-B interaction with neuropilin-1 had no effect. Surprisingly, in rats, the heart-specific VEGF-B transgene induced impressive growth of the epicardial coronary vessels and their branches, with large arteries also seen deep inside the subendocardial myocardium. However, VEGF-B, unlike other VEGF family members, did not induce significant capillary angiogenesis, increased permeability, or inflammatory cell recruitment.

Conclusions: VEGF-B appears to be a coronary growth factor in rats but not in mice. The signals for the VEGF-B-induced cardiac hypertrophy are mediated at least in part via the endothelium. Because cardiomyocyte damage in myocardial ischemia begins in the subendocardial myocardium, the VEGF-B-induced increased arterial supply to this area could have therapeutic potential in ischemic heart disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Capillary Permeability / physiology*
  • Cardiomegaly / physiopathology
  • Coronary Vessels / growth & development*
  • Female
  • Humans
  • Inflammation / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Models, Animal
  • Muscle, Skeletal / blood supply
  • Myocardium
  • Neovascularization, Physiologic / physiology*
  • Neuropilin-1 / physiology
  • Rats
  • Rats, Transgenic
  • Rats, Wistar
  • Vascular Endothelial Growth Factor B / genetics
  • Vascular Endothelial Growth Factor B / physiology*


  • Vascular Endothelial Growth Factor B
  • Neuropilin-1