- Vascular Endothelial Growth Factor-B (VEGF-B) is a member of the VEGF family of signaling proteins, but unlike VEGF-A, it is not a major driver of angiogenesis. Instead, VEGF-B has a more specialized role, particularly in vascular survival, metabolic regulation, and cardiac physiology. VEGF-B binds primarily to VEGFR-1 (Flt-1) and to the co-receptor neuropilin-1 (NRP-1), but not significantly to VEGFR-2, which explains why its angiogenic activity is limited compared to VEGF-A.
- VEGF-B exists in two major isoforms generated by alternative splicing: VEGF-B167 and VEGF-B186. These isoforms differ in their binding properties and tissue distribution. VEGF-B is highly expressed in metabolically active tissues such as the heart, skeletal muscle, and brown adipose tissue, suggesting a role beyond angiogenesis—specifically in energy metabolism and tissue protection. Experimental studies show that VEGF-B supports endothelial cell survival and helps maintain vascular integrity, particularly in the coronary vasculature, rather than strongly stimulating new vessel growth.
- Functionally, VEGF-B contributes to the protection of tissues against ischemic injury. In the heart and brain, it has been shown to reduce apoptosis of endothelial cells and promote cell survival under stress conditions, such as ischemia or hypoxia. Another important aspect of VEGF-B biology is its role in fatty acid uptake and transport. By signaling through VEGFR-1 and NRP-1 on endothelial cells, VEGF-B regulates the expression of fatty acid transport proteins, influencing the uptake of lipids into tissues like the myocardium. This suggests VEGF-B is involved in coordinating vascular function with metabolic needs.
- Clinically and pathologically, VEGF-B does not play as prominent a role in cancer or ocular diseases compared to VEGF-A. However, it has been investigated for its therapeutic potential in cardiovascular and metabolic diseases. In ischemic heart disease, VEGF-B–based therapies are being explored for their ability to enhance myocardial perfusion and protect cardiac tissue without inducing excessive angiogenesis, which can sometimes complicate VEGF-A therapy. Its role in lipid metabolism has also attracted interest in obesity and metabolic disorders, although the exact clinical applications remain under investigation.
