Hypoxia differentially regulates VEGFR1 and VEGFR2 levels and alters intracellular signaling and cell migration in endothelial cells

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• 作者：Clare Ulyatt^a ; John Walker^a ; Sreenivasan Ponnambalam ; ^a ; ^{s.ponnambalam@leeds.ac.uk}
• 关键词：Hypoxia ; VEGF-A ; VEGFR1 ; VEGFR2 ; Endothelial ; Signaling
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：21 January 2011
• 年：2011
• 卷：404
• 期：3
• 页码：774-779
• 全文大小：412 K

文摘

The role of hypoxia on endothelial cell function and response to growth factors is unknown. Here, we tested the hypothesis that hypoxia re-programs endothelial function by modulating vascular endothelial growth factor receptor levels which in turn alter intracellular signaling and cell function. Hypoxia stimulated VEGF-A and VEGFR1 expression but decreased VEGFR2 levels in endothelial cells. During hypoxia, plasma membrane VEGFR1 levels were elevated whereas VEGFR2 levels were depleted. One functional consequence of hypoxia is a reduction in VEGF-A-stimulated and VEGFR2-regulated intracellular signaling including lowered endothelial nitric oxide synthase activation. Venous, arterial and capillary endothelial cells subjected to hypoxia all exhibited reduced cell migration in response to VEGF-A. A mechanistic explanation is that VEGFR1:VEGFR2 ratio is substantially increased during hypoxia to block VEGF-A-stimulated and VEGFR2-regulated endothelial responses to maximize cell viability and recovery.