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J Thromb Haemost ; 22(7): 1919-1935, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38453025

RESUMO

BACKGROUND: Coagulopathy is a major cause of morbidity and mortality in COVID-19 patients. Hypercoagulability in COVID-19 results in deep vein thrombosis, thromboembolic complications, and diffuse intravascular coagulation. Microbiome dysbiosis influences the clinical course of COVID-19. However, the role of dysbiosis in COVID-19-associated coagulopathy is not fully understood. OBJECTIVES: The present study tested the hypothesis that the microbiota-derived proapoptotic corisin is involved in the coagulation system activation during SARS-CoV-2 infection. METHODS: This cross-sectional study included 47 consecutive patients who consulted for symptoms of COVID-19. A mouse acute lung injury model was used to recapitulate the clinical findings. A549 alveolar epithelial, THP-1, and human umbilical vein endothelial cells were used to evaluate procoagulant and anticoagulant activity of corisin. RESULTS: COVID-19 patients showed significantly high circulating levels of corisin, thrombin-antithrombin complex, D-dimer, tumor necrosis factor-α, and monocyte-chemoattractant protein-1 with reduced levels of free protein S compared with healthy subjects. The levels of thrombin-antithrombin complex, D-dimer, and corisin were significantly correlated. A monoclonal anticorisin-neutralizing antibody significantly inhibited the inflammatory response and coagulation system activation in a SARS-CoV-2 spike protein-associated acute lung injury mouse model, and the levels of corisin and thrombin-antithrombin complex were significantly correlated. In an in vitro experiment, corisin increased the tissue factor activity and decreased the anticoagulant activity of thrombomodulin in epithelial, endothelial, and monocytic cells. CONCLUSION: The microbiota-derived corisin is significantly increased and correlated with activation of the coagulation system during SARS-CoV-2 infection, and corisin may directly increase the procoagulant activity in epithelial, endothelial, and monocytic cells.


Assuntos
Coagulação Sanguínea , COVID-19 , Células Endoteliais da Veia Umbilical Humana , SARS-CoV-2 , Humanos , COVID-19/sangue , COVID-19/complicações , COVID-19/imunologia , Animais , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Camundongos , Células A549 , Lesão Pulmonar Aguda/microbiologia , Lesão Pulmonar Aguda/sangue , Células THP-1 , Idoso , Modelos Animais de Doenças , Microbiota , Disbiose , Adulto , Antitrombina III , Camundongos Endogâmicos C57BL , Peptídeo Hidrolases
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