@article {43,
	title = {Vascular endothelial growth factor-B acts as a coronary growth factor in transgenic rats without inducing angiogenesis, vascular leak, or inflammation},
	journal = {Circulation},
	volume = {122},
	year = {2010},
	month = {2010/Oct/},
	pages = {1725 - 33},
	abstract = {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.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/20937974},
	author = {Bry, Maija and Kivel{\"a}, Riikka and Holopainen, Tanja and Anisimov, Andrey and Tammela, Tuomas and Soronen, Jarkko and Silvola, Johanna and Saraste, Antti and Jeltsch, Michael and Korpisalo, Petra and Carmeliet, Peter and Lemstr{\"o}m, Karl B and Shibuya, Masabumi and Yl{\"a}-Herttuala, Seppo and Alhonen, Leena and Mervaala, Eero and Andersson, Leif C and Knuuti, Juhani and Alitalo, Kari}
}
