Functional Upregulation of the Vascular Endothelial Growth Factor Receptor KDR by Hypoxia

Abstract

These data indicate that hypoxia stimulates VEGF-dependent signaling not only by upregulation of VEGF ligand but also by functional upregulation of a specific signaling receptor. Therefore, these data provide evidence that the endothelium plays an active role in hypoxia-induced angiogenesis.

Phosphorylated KDR expression in endometrial cancer cells relates to HIF1α/VEGF pathway and unfavourable prognosis

“…Gerber et al 34 showed that, in contrast to the flt-1 receptor, KDR is not induced by hypoxia. However, this finding contrasts to Waltenberger et al's 35 earlier report, where hypoxia upregulated the expression of KDR in the endothelial cells of umbilical veins. Upregulation of VEGF and KDR, which is paralleled by HIF1a expression, has also been recorded in rabbit skeletal muscle during acute hypoxia.…”

Postnatal bone marrow stromal cells elicit a potent VEGF-dependent neoangiogenic response in vivo

“…Although serum from animals with an acute myocardial infarct will stimulate proliferation of endothelial precursors, 25 our experimental model was devoid of ischemic organ injury and a serum-bound MSC transdifferentiation factor is unlikely. Since the VEGF gene is hypoxiaresponsive, 31 and we demonstrated de novo VEGF production by MSCs in vivo, we speculate that reduced oxygen tension milieu of Matrigel implant may provide the stimulus required to promote VEGF production by MSCs. We propose that VEGF production by MSCs occurs as part of an adaptive response to the relative hypoxia of the Matrigel milieu in vivo.…”

VEGFR1 and VEGFR2 in Alzheimer’s Disease

“…Studies of VEGFR2 expression in animal models of brain ischemia and in vitro models of neuronal or brain tissue hypoxia have yielded conflicting results. In some, VEGFR2 was upregulated [69][70][71][72][73] and in others, decreased [74][75][76]. Other factors that may account for the reduced or unchanged microvessel density in hyperperfused cortex in AD [3] include sequestration of VEGF by Aβ42 [55], the decreased VEGFR1:sVEGFR1 ratio (see above), and binding of Aβ42 to VEGFR2 -shown by Patel et al [2010] to block VEGF-mediated signaling.…”