Blood flow patterns switch VEGFR2 activity through differential S-nitrosylation and S-oxidation.

ABSTRACT: Vascular endothelial growth factor receptor-2 (VEGFR2) plays a key role in maintaining vascular endothelial homeostasis. Here, we show that blood flows determine activation and inactivation of VEGFR2 through selective cysteine modifications. VEGFR2 activation is regulated by reversible oxidation at Cys¹²⁰⁶ residue. H₂O₂-mediated VEGFR2 oxidation is induced by oscillatory flow in vascular endothelial cells through the induction of NADPH oxidase-4 expression. In contrast, laminar flow induces the expression of endothelial nitric oxide synthase and results in the S-nitrosylation of VEGFR2 at Cys¹²⁰⁶, which counteracts the oxidative inactivation. The shear stress model study reveals that disturbed blood flow operated by partial ligation in the caroti

SUBMITTER: Kang DH 

PROVIDER: S-EPMC11869325 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature