Angiogenesis is critical to
wound repair. Newly formed blood vessels participate in provisional granulation tissue formation and provide nutrition and
oxygen to growing tissues. In addition, inflammatory cells require the interaction with and transmigration through the endothelial basement membrane to enter the site of injury. Angiogenesis, in response to tissue injury, is a dynamic process that is highly regulated by signals from both serum and the surrounding extracellular matrix (ECM) environment.
Vascular endothelial growth factor,
angiopoietin,
fibroblast growth factor, and
transforming growth factor beta are among those most potent angiogenic
cytokines in
wound angiogenesis. The cooperative regulation of them is essential for
wound repair. Migration of endothelial cells and development of new capillary vessels during
wound repair is dependent on not only the cells and
cytokines present but also the production and organization of ECM components both in granulation tissue and in endothelial basement membrane. The ECM regulates angiogenesis by providing scaffold support and signaling roles. They also serve as a reservoir and modulator for
growth factors. Laminins are the major noncollagenous ECM of endothelial basement membrane. Two newly recognized laminins, 8 and 10, are the major laminins produced by human dermal microvascular endothelial cells.
Laminin 10 is highly expressed in blood vessels around skin
wounds.
Laminin 8 promotes dermal endothelial cell attachment, migration, and tubule formation.
Integrins with either beta 1 or alpha v subunits are the major cellular surface receptors for ECM molecules and mediate the interactions between cells and ECM during
wound angiogenesis.