Disseminated intravascular coagulation caused by moojenactivase, a procoagulant snake venom metalloprotease

Autor(es)

Sartim, Marco A. ; Cezarette, Gabriel N. ; Jacob-Ferreira, Anna L. ; Frantz, Fabiani G. ; Faccioli, Lucia H. ; Sampaio, Suely V.

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Macromolecules; v. 103, p. 1077-1086, OCT 2017.
• Citações Web of Science: 3

Resumo

Snake venom toxins that activate coagulation factors are key players in the process of venom-induced coagulopathy, and account for severe clinical manifestations. The present study applies a variety of biochemical, hematological, and histopathological approaches to broadly investigate the intravascular and systemic effects of moojenactivase (MooA), the first described Mild subclass metalloprotease isolated from Bothrops sp. venom that activates coagulation factors. MooA induced consumption coagulopathy with high toxic potency, characterized by prolongation of prothrombin and activated partial thromboplastin time, consumption of fibrinogen and the plasma coagulation factors X and II, and thrombocytopenia. MooA promoted leukocytosis and expression of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, accompanied by tissue factor-dependent procoagulant activity in peripheral blood mononuclear cells. This metalloprotease also caused intravascular hemolysis, elevated plasma levels of creatine kinase-MB, aspartate transaminase, and urea/creatinine, and induced morphopathological alterations in erythrocytes, heart, kidney, and lungs associated with thrombosis and hemorrhage. Diagnosis of MooA-induced disseminated intravascular coagulation represents an important approach to better understand the pathophysiology of Bothrops envenomation and develop novel therapeutic strategies targeting hemostatic disturbances. (C) 2017 Published by Elsevier B.V. (AU)

• Processo FAPESP: 15/06290-6 - Avaliação do potencial anti-inflamatório da crotoxina, uma fosfolipase A2 isolada da peçonha de Crotalus durissus terrificus, em modelo de coagulação intravascular disseminada induzida por endotoxemia
• Beneficiário: Marco Aurélio Sartim
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
• Beneficiário: Suely Vilela
• Modalidade de apoio: Auxílio à Pesquisa - Temático