Paper I
Question
Angiogenesis in tissue repair.
Answer
Angiogenesis is the formation of new blood vessels from pre-existing vasculature, an essential process in tissue repair that supplies oxygen and nutrients needed to sustain the metabolically active repair process and forms part of granulation tissue.
Steps of angiogenesis
- Vasodilatation of pre-existing vessels in response to nitric oxide, and increased permeability induced by VEGF
- Degradation of the basement membrane of the parent vessel by proteases, allowing endothelial cells to migrate
- Migration of endothelial cells toward the area of tissue injury (guided by angiogenic factors)
- Proliferation of endothelial cells just behind the migrating leading front
- Maturation of endothelial cells, including inhibition of proliferation and remodelling into capillary tubes
- Recruitment of periendothelial cells (pericytes for capillaries, smooth muscle cells for larger vessels) to support the newly formed tube
Key growth factors/mediators
- Vascular endothelial growth factor (VEGF): Principal driver of angiogenesis, stimulating both migration and proliferation of endothelial cells
- Fibroblast growth factor (FGF-2): Promotes proliferation of endothelial cells and other cell types
- Angiopoietins (Ang1, Ang2) and their Tie2 receptor: Involved in vessel maturation and stabilization
- Platelet-derived growth factor (PDGF): Recruits pericytes/smooth muscle cells
Clinical significance
- Essential for wound healing and formation of granulation tissue
- Also relevant pathologically in tumour growth (tumour angiogenesis) and chronic inflammatory conditions