Reactive Oxygen Species in Vascular Formation and Development
Figure 2
ROS in VEGF signaling in endothelial cell proliferation and migration. Binding of VEGF to VEGFR2 stimulates ROS production via Rac-1 mediated NADPH oxidase activation and through increased mitochondria activity. ROS oxidize and inactivate protein tyrosine phosphatases (PTPs), disinhibiting their negative regulation on downstream signaling pathways, such as Src/PI3K/Akt and PLC/PKC/Raf/ERK. H2O2 are also generated extracellularly by ecSOD to locally inactivate DEP1 and PTP1B, two PTPs that dephosphorylate VEGF receptor, thereby promoting VEGF-induced VEGFR2 autophosphorylation. Through induction of transcription factors HIF-1, ROS can also upregulate VEGF secretion and VEGFR expression.
