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

M Bry, R Kivelä, T Holopainen, A Anisimov… - Circulation, 2010 - Am Heart Assoc
M Bry, R Kivelä, T Holopainen, A Anisimov, T Tammela, J Soronen, J Silvola, A Saraste…
Circulation, 2010Am Heart Assoc
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-B167 isoform, transgenic …
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-B167 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.
Am Heart Assoc