Heme oxygenase-1 inhibits DENV-induced endothelial hyperpermeability and serves as a potential target against dengue hemorrhagic fever.
FASEB J
; 36(1): e22110, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34918393
Dengue virus (DENV) is a cause of vascular endothelial dysfunction and vascular leakage, which are characterized as hallmarks of dengue hemorrhagic fever or dengue shock syndrome, which become a severe global health emergency with substantial morbidity and mortality. Currently, there are still no promising therapeutics to alleviate the dengue-associated vascular hemorrhage in a clinical setting. In the present study, we first observed that heme oxygenase-1 (HO-1) expression level was highly suppressed in severe DENV-infected patients. In contrast, the overexpression of HO-1 could attenuate DENV-induced pathogenesis, including plasma leakage and thrombocytopenia, in an AG129 mouse model. Our data indicate that overexpression of HO-1 or its metabolite biliverdin can maintain endothelial integrity upon DENV infection in vitro and in vivo. We further characterized the positive regulatory effect of HO-1 on the endothelial adhesion factor vascular endothelial-cadherin to decrease DENV-induced endothelial hyperpermeability. Subsequently, we confirmed that two medicinal plant-derived compounds, andrographolide, and celastrol, widely used as a nutritional or medicinal supplement are useful to attenuate DENV-induced plasma leakage through induction of the HO-1 expression in DENV-infected AG129 mice. In conclusion, our findings reveal that induction of the HO-1 signal pathway is a promising option for the treatment of DENV-induced vascular pathologies.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Permeabilidade Capilar
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Endotélio Vascular
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Dengue Grave
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Vírus da Dengue
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Heme Oxigenase-1
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Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
FASEB J
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Taiwan