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In health, tightly positioned NOX-derived H 2 O 2 transiently oxidizes catalytic or regulatory cysteines on kinases and phosphatases to tune pathways controlling proliferation, migration and host defense, whereas chronic or dysregulated activitydriven by inflammatory cytokines, mechanical stress, hyperglycemia, or angiotensin IIamplifies redox tone, quenches nitric oxide and promotes endothelial dysfunction, vascular and tissue fibrosis and heightened innate immune priming (Kraun et al