Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium

Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1614-20. doi: 10.1161/ATVBAHA.107.158725. Epub 2008 May 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / metabolism
  • Animals
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism*
  • Coronary Vessels / physiopathology
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Genetic Therapy / methods
  • Hindlimb
  • Ischemia / metabolism*
  • Ischemia / pathology
  • Ischemia / physiopathology
  • Ischemia / therapy
  • Lung / blood supply
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Muscle, Skeletal / blood supply
  • Myocardial Ischemia / metabolism*
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / physiopathology
  • Myocardial Ischemia / therapy
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Neovascularization, Physiologic* / drug effects
  • Recombinant Proteins / metabolism
  • Retinal Vessels / metabolism
  • Skin / blood supply
  • Up-Regulation
  • Vascular Endothelial Growth Factor B / administration & dosage
  • Vascular Endothelial Growth Factor B / deficiency
  • Vascular Endothelial Growth Factor B / genetics
  • Vascular Endothelial Growth Factor B / metabolism*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

  • Angiogenesis Inducing Agents
  • Recombinant Proteins
  • VEGFB protein, human
  • Vascular Endothelial Growth Factor B
  • vascular endothelial growth factor B, mouse
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1