Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway
Biomolecules & Therapeutics
; : 474-483, 2019.
Article
em En
| WPRIM
| ID: wpr-763034
Biblioteca responsável:
WPRO
ABSTRACT
Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.
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Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Permeabilidade
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Fosforilação
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Retinaldeído
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Permeabilidade Capilar
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Corioide
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Actinas
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Neovascularização de Coroide
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Receptores de Fatores de Crescimento do Endotélio Vascular
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Células Endoteliais
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Fator A de Crescimento do Endotélio Vascular
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biomolecules & Therapeutics
Ano de publicação:
2019
Tipo de documento:
Article