T.I. Gavrilenko, N.A. Ryzhkova, A.N. ParkhomenkoVascular endothelial growth factor in the clinic of internal diseases and its pathogenetic value

Vascular endothelial growth factor (VEGF) is a multifunctional cytokine produced by various cells, including vascular smooth cells, endothelial and inflammatory cells. Expression of VEGF is stimulated in a number of proangiogenic factors, and depends also on such factors of environment as рН, pressure and concentrations of oxygen. The several subtypes of VEGF, which can partly explain multiplicity of biological effects of VEGF, are described: placenta-derived growth factor (PIGF), VEGF-А, VEGF-C, D, c-fos-induced growth factor (FIGF). VEGF influences selectively on vascular endothelium, providing its stability, promoting proliferation, migration and forming of tubules of endothelial cells. VEGF plays an important regulator role, promoting expression of endothelial adhesion factors and modulating adhesion of leucocytes and thrombocytes, thus regulating migration of endothelial cells and expression of matrix metalloproteinases. VEGF co-operates with еNOS in caveols of normal endothelial cells, regulating its activity and therefore promoting the products of NO and prostacyclin, and also through activation of phospholypase A2. Participation of VEGF is shown in some pathological processes. Considerable attention is given to the role of VEGF at atherosclerosis and ischemic heart disease. This factor can considered be, from one side, a vascular protector, operating through stimulation of products of NО and PGI2, lowering LDL toxicity, inhibiting proliferation of vascular smooth cells, mediating antiapoptotic effect and promoting the survival of endothelium, and increasing its antithrombotic and antiinflammatory properties. From the other side, VEGF can be a harmful factor, mediating neovascularisation of atherosclerotic plaque, which results in its instability. VEGF expression has been noted in human atherosclerotic plaque. The capability of VEGF to stimulate monocyte/macrophage influx into the vessel wall suggests that it may contribute to atherogenesis. In contrast, human clinical trial experience has provided no evidence to support the concept that administration of angiogenic agents to patients with advanced atherosclerosis will lead to disease progression. Direction of action of VEGF depends on many factors, in particular, on scene of action, specific for disease or features of therapeutic interferences, and also on the level of expression of other cytokines in response to pathological process.

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