High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis

Up‐regulated basigin‐2 in microglia induced by hypoxia promotes retinal angiogenesis

“…This might be a rational explanation of the finding that VEGF expression alterations are not in accordance with VEGFR‐2 in RF/6A cells. VEGFR‐2 is the main receptor VEGF exerts its angiogenic effects 35, 36, 37. Our results reveal that IGF‐1, being secreted by hypoxic BV2 to the local microenvironment, stimulates VEGFR‐2 transcription and expression in RF/6A and induces the resultant angiogenesis.…”

Increased revascularization efficacy after administration of an adenovirus encoding VEGF121

“…32,33 VEGF binds to two highly specific tyrosine kinase receptors, Flt-1 and KDR/Flk-1, found almost exclusively on endothelial cells. [34][35][36] Following receptor binding, endothelial cells are stimulated to proliferate and form tube-like structures, the first steps in forming new blood vessels, a process known as angiogenesis. 37,38 Preclinical studies have demonstrated that delivery of the VEGF gene into ischemic tissue can stimulate the development of collateral arteries in animal models of peripheral and myocardial ischemia.…”

Placenta growth factor stimulates MAP kinase and mitogenicity but not phospholipase C-γ and migration of endothelial cells expressing Flt 1

“…Based on their structure, it is reasonable to assume that both KDR and Flt 1 are activated in agreement with the general scheme for receptor tyrosine kinases. KDR has been shown to autophosphorylate in response to VEGF (Millauer et al, 1993;Terman et al, 1992) and four autophosphorylation sites (Y951, Y996, Y1054 and Y1059) have been identi®ed in vitro, in the KDR intracellular domain (Dougher-Vermazen et al, 1994). In contrast, VEGF stimulation leads only to very weak Flt 1 autophosphorylation (de Vries et al, 1992;Waltenberger et al, 1994).…”