title: Vascular endothelial growth factor-B in physiology and disease.
abstract: Vascular endothelial growth factor-B (VEGF-B), discovered over 15 years ago, has long been seen as one of the more ambiguous members of the VEGF family. VEGF-B is produced as two isoforms: one that binds strongly to heparan sulfate in the pericellular matrix and a soluble form that can acquire binding via proteolytic processing. Both forms of VEGF-B bind to VEGF-receptor 1 (VEGFR-1) and the neuropilin-1 (NRP-1) coreceptor, which are expressed mainly in blood vascular endothelial cells. VEGF-B-deficient mice and rats are viable without any overt phenotype, and the ability of VEGF-B to induce angiogenesis in most tissues is weak. This has been a puzzle, as the related placenta growth factor (PlGF) binds to the same receptors and induces angiogenesis and arteriogenesis in a variety of tissues. However, it seems that VEGF-B is a vascular growth factor that is more tissue specific and can have trophic and metabolic effects, and its binding to VEGFR-1 shows subtle but important differences compared with that of PlGF. VEGF-B has the potential to induce coronary vessel growth and cardiac hypertrophy, which can protect the heart from ischemic damage as well as heart failure. In addition, VEGF-B is abundantly expressed in tissues with highly active energy metabolism, where it could support significant metabolic functions. VEGF-B also has a role in neuroprotection, but unlike other members of the VEGF family, it does not have a clear role in tumor progression. Here we review what is hitherto known about the functions of this growth factor in physiology and disease.
authors.affiliation: Wihuri Research Institute and Translational Cancer Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Maija
authors.initials: M
authors.lastname: Bry
authors.affiliation: Wihuri Research Institute and Translational Cancer Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Kivelä
authors.affiliation: Wihuri Research Institute and Translational Cancer Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Leppänen
authors.affiliation: Wihuri Research Institute and Translational Cancer Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
mesh_terms: D000818:Animals; D004194:Disease; D006801:Humans; D015394:Molecular Structure; D042561:Vascular Endothelial Growth Factor B / Q000737:chemistry / Q000502:physiology*
chemical_list: D042561:Vascular Endothelial Growth Factor B