Angiogenesis And Arteriogenesis

Neovascularization, the formation of new blood vessels, is inherent in vascular tissue, and it can be induced by trauma, ischemia, inflammation or tumour growth [1]. The creation of new blood vessels is dependent on a complicated interaction between local produced cytokines and cell derived from the tissue area and the blood circulation [1].

However, the vascular growth factors are of crucial importance for the neovascu-larization, which can be divided into three processes: angiogenesis, vasculogenesis and arteriogenesis. Angiogenesis is the formation of new capillaries by sprouding from the existing capillary net, probably from the postcapillary venules [2]; arteriogenesis is the transformation of pre-existing arterioles/collaterales into small muscular arteries and/or de novo formation of new vessels with a tunica media [3,4]; and vasculogenesis is the formation of new vessels from multipotent endothelial stem cells [1, 5-7]. Angiogenesis, arteriogenesis and vasculogenesis are functional connected phenomenon's, which cannot be separated. Formation of new capillaries (angiogenesis) without simultaneously formation of larger arteries for supplying the capillaries is without any meaning.

Angiogenesis in the tissue can be initiated by local production and liberation of vascular growth factors. Many different vascular growth factors have now been discovered, which can induce angiogenesis by stimulation of growth and migration of endothelial cells [1]. The vascular growth factors are polypeptides, initially isolated in studies of tumour growth. These proteins are responsible for normal as well as pathological vessel growth. For therapeutic treatment in myocardial ischemia, the most used proteins have been members of the fibroblast growth factor (FGF) family and the vascular endothelial growth factor (VEGF) family. FGF induce vascular growth by binding to receptors at the surface of the endothelial cells. However, receptors for FGF are also located on other cell types, e.g. fibroblasts. VEGF binds to receptors, which mainly are located on the endothelial cells. Presently, VEGF-A and VEGF-C are the two factors with the greatest clinical impact in the adult man. VEGF-C is important for growth of lymphatics, while VEGF-A is of importance for angiogenesis. VEGF-A can be divided into five isoformes with 121, 145, 165, 189, and 206 amino acids. Both VEGF and FGF have in animal studies induced angiogenesis and arteriogenesis with formation of new capillaries and arteries in ischemic myocardium [1, 8, 9].

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