Vascular endothelial growth factor - basic science and its clinical implications  Peter Celec, Yoshikazu Yonemitsu  Pathophysiology  Volume 11, Issue 2, Pages 69-75 (October 2004) DOI: 10.1016/j.pathophys.2004.03.002 Copyright © 2004 Elsevier Ireland Ltd Terms and Conditions

Fig. 1 Molecular interactions in VEGF signaling pathways in endothelial cells. Ischemic tissue produces various cytokines and under hypoxic conditions also HIF-1α. These signal molecules activate the expression or the release of VEGF that binds to VEGFR. With a number of intermediates, that for the most part have been described, VEGF serves both an angiogenic stimulant and a survival factor for the existing vessels. The formation of new vessels (angiogenesis, vasculogenesis or neovascularization) results from altered gene expression and modification of the cell cycle - proliferation of the relevant pluripotent cell types. Especially vasoprotective compounds such as PGI2 and NO mediate inhibition of obliteration in existing blood vessels. Both signaling molecules inhibit platelet aggregation and leukocyte adhesion and, thus, inhibit thrombosis and atherosclerotic plaque progression. Abbreviations: AA: arachidonic acid; COX-1: cyclooxygenase-1; cPLA2: cytosolic phospholipase A2; DAG: diacylglycerol; eNOS-P: activated endothelial NO synthase; ERK: extracellular signal regulated kinase; IP3: inositol 1,4,5-triphosphate; PGI2: prostacyclin; PGIS: PGI synthase; PI3K: phosphatidylinositol 3-kinase; PKC: protein kinase C; and PLC-γ: phospholipase C. Pathophysiology 2004 11, 69-75DOI: (10.1016/j.pathophys.2004.03.002) Copyright © 2004 Elsevier Ireland Ltd Terms and Conditions