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

Dong Hoon Kang, Yerin Kim, Seongchun Min, Su Youn Lee, Ka Young Chung, In Jeoung Baek, Kihwan Kwon, Hanjoong Jo, Sang Won Kang

Research output: Contribution to journalArticlepeer-review


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 carotid arteries induces endothelial damage and intimal hyperplasia in control mice but not in knock-in mice harboring the oxidation-resistant mutant (C1206S) of VEGFR2. Thus, our findings reveal that flow-dependent redox regulation of the VEGFR2 kinase is critical for the structural and functional integrity of the arterial endothelium.

Original languageEnglish
Article number113361
JournalCell Reports
Issue number11
StatePublished - 28 Nov 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)


  • CP: Cell biology
  • NOX4
  • VEGFR2
  • endothelial NOS
  • endothelial cells
  • shear stress


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