Research ArticleCell Biology

A Ligand-Independent VEGFR2 Signaling Pathway Limits Angiogenic Responses in Diabetes

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Science Signaling  07 Jan 2014:
Vol. 7, Issue 307, pp. ra1
DOI: 10.1126/scisignal.2004235

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How High Blood Sugar Suppresses Angiogenesis

Individuals with diabetes are prone to developing damage to both small and larger blood vessels, which can lead to complications such as blindness and strokes. When bound to VEGF (vascular endothelial growth factor), VEGFR2 (VEGF receptor 2) promotes the formation of new blood vessels, a process called angiogenesis, which is impaired in diabetic individuals. Warren et al. found that endothelial cells from a mouse model of diabetes showed reduced cell surface abundance of VEGFR2 and responsiveness to VEGF. Hyperglycemia generates reactive oxygen species (ROS), which can activate the Src family of kinases (SFKs). The authors showed that SFKs activated by ROS phosphorylated VEGFR2 in an intracellular compartment, reducing the abundance of VEGFR2 at the cell surface and thus restricting angiogenic responses. Treating diabetic mice with an antioxidant restored cell surface VEGFR2 and enabled activation of VEGFR2 by VEGF. Thus, angiogenic responses in diabetic individuals could be improved by limiting ROS generation or inhibiting SFKs.