Angiogenesis and early connective tissue deposition in wound healing
THE CONTEXT
Repair involves new vessel formation, fibroblast recruitment, and deposition of extracellular matrix (ECM), followed by maturation into a scar.
Control of angiogenesis
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Angiogenesis involves sprouting of new vessels from existing vessels. Vascular endothelial growth factor (VEGF) is the most important angiogenic factor described and stimulates endothelial cell migration and proliferation.
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Hypoxia increases hypoxia inducible factor (HIF), a transcription factor that regulates VEGF production. Cells such as macrophages produce VEGF in injured tissue in response to hypoxia.
Formation and maturation of vessels
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In response to VEGF, nearby intact vessels dilate and become permeable. Matrix metalloproteases digest the basement membrane, permitting a vascular sprout to form.
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Endothelial cells at the tip migrate toward the injury, while cells behind the tip proliferate and remodel into vascular tubes.
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Recruitment and remodeling of pericytes in capillaries or smooth muscle cells in larger vessels produce mature vessels.
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Progressive vascular regression transforms highly vascular granulation tissue into a pale, largely avascular scar.
Fibroblasts and ECM deposition
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Connective tissue deposition begins with fibroblast migration into the injury and proliferation, followed by production and deposition of ECM proteins.
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Locally produced cytokines and growth factors, including PDGF, FGF-2, and TGF-b, coordinate these processes. Inflammatory cells, particularly infiltrating macrophages, are major sources.
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Connective tissue consists of fibroblasts and an acellular ECM containing collagen and other glycoproteins.
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Cell–ECM interactions support healing and normal tissue architecture. The ECM provides mechanical support for cell anchorage and migration and helps maintain cell polarity.