Vascular endothelial growth factor B (VEGF-B) (VEGF-B)

Vascular endothelial growth factor B (VEGF-B) is a signaling protein in the VEGF family that plays a specialized role in metabolic regulation and cell survival rather than primary angiogenesis (Physiol Rev. 2014). Unlike VEGF-A, VEGF-B has a minimal role in promoting angiogenesis but is a potent survival factor and a key regulator of fatty acid transport from the blood into tissues such as the heart and skeletal muscle (Nature 2010). The protein exists in two major isoforms: VEGF-B167 and VEGF-B186, with the 167 isoform featuring a C-terminal heparan-sulfate binding site that facilitates its association with the extracellular matrix and cell surface proteoglycans (UniProt P49765). The heparan-sulfate binding site is critical for the localization and signaling efficiency of the VEGF-B167 isoform (Biochem Soc Trans. 2009). In disease states like type 2 diabetes, VEGF-B-mediated fatty acid uptake can lead to lipotoxicity and insulin resistance, making it a target for metabolic therapy (Nature 2012). Conversely, its survival-promoting effects are being explored for neuroprotection and treating ischemic heart disease (PNAS 2008). Therapeutic strategies include monoclonal antibodies like CSL311 and decoy receptors like aflibercept, which sequester the growth factor to modulate its metabolic and vascular effects (DrugBank DB08885). Targeting the specific heparan-sulfate binding site or the interaction with proteoglycans represents a potential strategy to selectively modulate the activity of the matrix-bound isoform (Curr Drug Targets 2010).

Other names

VEGFBVEGFLVRFVascular endothelial growth factor B167Vascular endothelial growth factor B186Heparin-binding VEGF-B

Inhibition of VEGF-B binding to VEGFR-1 and NRP-1; sequestration of the growth factor to prevent receptor activation and downstream fatty acid transport.