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Proposed scheme of Nox2 and Nox4-dependent VEGF-induced EC migration. Upon stimulation with VEGF, Nox4-derived H2O2 works upstream of Nox2 to stimulate production of superoxide (O2-•). VEGF also stimulates activation of eNOS to produce ·NO. Together, O2-• and ·NO cause S-glutathiolation of SERCA2b cysteine-674, increasing Ca2+ uptake into the endoplasmic reticulum and Ca2+ influx into the cytosol, stimulating EC migration.
