The biology of vascular endothelial growth factor-B (VEGF-B)

The formation of new blood vessels (angiogenesis) is critical for both embryonic development and a variety of normal postnatal physiological processes. Various pathological processes, most notably tumour growth and chronic inflammation, are also known to be dependent on the new vessel formation. Amongst the variety of factors that contribute to the regulation of this complex process, vascular endothelial growth factor (VEGF or VEGF-A) is arguably the most well characterised. The VEGF family of growth factors is now known to comprise of VEGF-A plus four additional members, including VEGF-B. In contrast to VEGF-A, surprisingly little is known about the precise biological role of VEGF-B. Unlike VEGF-A, which binds to the two receptor tyrosine kinases VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1/KDR), VEGF-B binds only to VEGFR-1 and the functional significance of VEGFR-1 signalling has remained problematic. More recently, however, evidence has emerged suggesting a key role for VEGFR-1 signalling in pathological angiogenesis and this has raised the possibility that, like VEGF-A, VEGFR-1 specific ligands such as VEGF-B may provide for novel therapeutic strategies and/or represent new therapeutic targets. Here we review current knowledge of the biology of VEGF-B. We note that although analysis to date, including expression profiling and the generation of gene targetted mice, has provided only limited insights, future studies using recently generated recombinant proteins and antagonist monoclonal antibodies should provide for a more comprehensive understanding.