Blood flow patterns switch VEGFR2 activity through differential S-nitrosylation and S-oxidation
- 주제(키워드) CP: Cell biology , endothelial cells , endothelial NOS , NOX4 , shear stress , VEGFR2
- 등재 SCIE, SCOPUS
- OA유형 Gold Open Access
- 발행기관 Elsevier B.V.
- 발행년도 2023
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000213394
- 본문언어 영어
- Published As https://doi.org/10.1016/j.celrep.2023.113361
- PubMed 37910508
초록/요약
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. © 2023 The Author(s)
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