Objective— The endogenous role of the VEGF family member vascular endothelial growth factor-B (VEGF-B) in pathological angiogenesis remains unclear.

Methods and Results— We studied the role of VEGF-B in various models of pathological angiogenesis using mice lacking VEGF-B (VEGF-B^−/−) or overexpressing VEGF-B₁₆₇. After occlusion of the left coronary artery, VEGF-B deficiency impaired vessel growth in the ischemic myocardium whereas, in wild-type mice, VEGF-B₁₆₇ overexpression enhanced revascularization of the infarct and ischemic border zone. By contrast, VEGF-B deficiency did not affect vessel growth in the wounded skin, hypoxic lung, ischemic retina, or ischemic limb. Moreover, VEGF-B₁₆₇ overexpression failed to enhance vascular growth in the skin or ischemic limb.

Conclusion— VEGF-B appears to have a relatively restricted angiogenic activity in the ischemic heart. These insights might offer novel therapeutic opportunities.