Author:

Keywords:

Angiogenesis Inducing Agents, Animals, Coronary Vessels, Disease Models, Animal, Gene Therapy, Gene Transfer Techniques, Hindlimb, Ischemia, Lung, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Nude, Muscle, Skeletal, Myocardial Ischemia, Myocardium, Neovascularization, Physiologic, Recombinant Proteins, Retinal Vessels, Skin, Up-Regulation, Vascular Endothelial Growth Factor B, Vascular Endothelial Growth Factor Receptor-1, Science & Technology, Life Sciences & Biomedicine, Hematology, Peripheral Vascular Disease, Cardiovascular System & Cardiology, VEGF-B, angiogenesis, arteriogenesis, collateral growth, cardiac ischemia, limb ischemia, ENDOTHELIAL GROWTH-FACTOR, ANGIOGENESIS, EXPRESSION, TISSUES, PLGF, Genetic Therapy, 1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, Cardiovascular System & Hematology, 3201 Cardiovascular medicine and haematology, 3202 Clinical sciences

Abstract:

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-B(167). After occlusion of the left coronary artery, VEGF-B deficiency impaired vessel growth in the ischemic myocardium whereas, in wild-type mice, VEGF-B(167) 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-B(167) overexpression failed to enhance vascular growth in the skin or ischemic limb. CONCLUSIONS: VEGF-B appears to have a relatively restricted angiogenic activity in the ischemic heart. These insights might offer novel therapeutic opportunities.