ENDOTHELIAL PROGENITOR CELLS

Process of blood vessels formation (i.e., vascularization) inside of tissues comprises different mechanism. In adulthood these processes can occur through different developmental processes.

The term vasculogenesis covers formation of blood vessels in situ or remodelling of pre-existing blood vessels. This process leads to differentiation of angioblasts or endothelial progenitor cells into endothelial cells.

Angiogenesis means de novo capillary formation by endothelial cells of pre-existing capillaries or post-capillary venules. Basic mechanisms participating in angiogenesis include endothelial sprouting (Fig. 6 on left), migration, proliferation, proteolysis of extracellular matrix, tube formation followed by vascular wall remodelling.

Fig. 6. Schematic drawing of angiogenesis. Image on left explains the effect of VEGF (vascular endothelial factor) released by growing tumour in activation of adjacent endothelial cells. Changes in phenotype of endothelial cells occur through expression of different molecules participating in angiogenesis.

Arteriogenesis comprises de novo formation of arteries and growth of collateral arteries. Main mechanisms responsible for arteriogenesis include vascular wall cell proliferation, migration and wall remodelling. Fluid shear stress acts as an inductor that triggers arteriogenesis by activating the endothelium, which results in expression of adhesive molecule MCP-1, which enables mononuclear cells (monocytes and lymphocytes) to invade and initiate the inflammation. These changes are followed by the proliferative phase when mitotic division occur in endothelial and smooth muscle cells. This is followed by remodelling phase that transforms a thin-walled blood vessel to an artery with the help of proteolysis of extracellular matrix, destruction of inner elastic membrane, cell migration and formation of the neointima. New space for the growth of a new artery is obtained by lysis of the neighbouring tissue and cell death. Remodelation is finished by synthesis of new extracellular matrix components.