Angiogenesis in Health and Disease

Angiogenesis

• Critical in healing at sites of injury, development of collateral circulations at sites of ischemia, and tumor growth beyond original blood supply
• Involves sprouting of new vessels from existing ones, consisting of:
  • Vasodilation in response to nitric oxide and increased permeability induced by VEGF
  • Separation of pericytes from the abluminal surface and breakdown of the basement membrane
  • Migration of endothelial cells toward the area of tissue injury
  • Proliferation of endothelial cells just behind the leading front of migrating cells
  • Recruiting pericytes for small capillaries and smooth muscle cells for larger vessels to form mature vessel
  • Suppression of endothelial proliferation and migration and deposition of the basement membrane

Signaling Pathways and Growth Factors

• Vascular endothelial growth factors (VEGFs), mainly VEGF-A, stimulate both migration and proliferation of endothelial cells, initiating capillary sprouting
• Fibroblast growth factors (FGFs), mainly FGF-2, stimulate proliferation of endothelial cells and migration of macrophages and fibroblasts to the damaged area
• Angio-poietins 1 and 2 (Ang 1 and Ang 2) play a role in angiogenesis and structural maturation of new vessels
• PDGF recruits smooth muscle cells and TGF-ß suppresses endothelial proliferation and migration, and enhances production of ECM proteins

Notch Signaling

• Regulates sprouting and branching of new vessels through "cross-talk" with VEGF
• Ensures proper spacing of new vessels to effectively supply healing tissue with blood