CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation

Bruno R. Salu; Rodrigo S. Ferreira; Marlon V. Brito; Tatiana F. Ottaiano; José Walber M.C. Cruz; Mariana Cristina C. Silva; Maria Tereza S. Correia; Patrícia M.G. Paiva; Francisco Humberto A. Maffei; Maria Luiza Vilela Oliva

doi:10.1515/hsz-2014-0127

Article

CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation

Bruno R. Salu , Rodrigo S. Ferreira , Marlon V. Brito , Tatiana F. Ottaiano , José Walber M.C. Cruz , Mariana Cristina C. Silva , Maria Tereza S. Correia , Patrícia M.G. Paiva , Francisco Humberto A. Maffei and Maria Luiza Vilela Oliva

Published/Copyright: August 6, 2014

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From the journal Biological Chemistry Volume 395 Issue 9

Abstract

Arterial thrombosis is an important complication of diabetes and cancer, being an important target for therapeutic intervention. Crataeva tapia bark lectin (CrataBL) has been previously shown to have hypoglycemiant effect and also to induce cancer cell apoptosis. It also showed inhibitory activity against Factor Xa (K_iapp=8.6 μm). In the present study, we evaluated the anti-thrombotic properties of CrataBL in arterial thrombosis model. CrataBL prolongs the activated partial thromboplastin time on human and mouse plasma, and it impairs the heparin-induced potentiation of antithrombin III and heparin-induced platelet activation in the presence of low-dose ADP. It is likely that the dense track of positive charge on CrataBL surface competes with the heparin ability to bind to antithrombin III and to stimulate platelets. In the photochemically induced thrombosis model in mice, in the groups treated with 1.25, 5.0, or 10 mg/kg CrataBL, prior to the thrombus induction, the time of total artery occlusion was prolonged by 33.38%, 65%, and 66.11%, respectively, relative to the time of the control group. In contrast to heparin, the bleeding time in CrataBL-treated mice was no longer than in the control. In conclusion, CrataBL was effective in blocking coagulation and arterial thrombus formation, without increasing bleeding time.

Keywords: antithrombin III; blood coagulation; heparin; Kallikrein; Kunitz inhibitor; lectin; thrombosis

Corresponding authors: Francisco Humberto A. Maffei, Departamento de Cirurgia e Ortopedia, Faculdade de Medicina de Botucatu, UNESP, 18618-970 Botucatu, SP, Brazil; and Centro de Estudos e Pesquisas, Hospital Santa Catarina, 01310-000 SP, Brazil, e-mail: fhmaffei@uol.com.br; and Maria Luiza Vilela Oliva, Departamento de Bioquímica, Universidade Federal de São Paulo, Rua três de Maio, 100, 04044-020 São Paulo, SP, Brazil, e-mail: olivaml.bioq@epm.br

aBruno R. Salu and Rodrigo S. Ferreira contributed equally to this article.

Acknowledgments

We thank Dr. Alexander Wlodawer for critical reading of this manuscript. We acknowledge the support of Fundação de Amparo à Pesquisa do Estado de São Paulo Grant 2009/53766-5, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Conflict of interest statement: The authors declare that no conflict of interest exists.

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Received: 2014-2-13

Accepted: 2014-6-25

Published Online: 2014-8-6

Published in Print: 2014-9-1

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Articles in the same Issue

https://doi.org/10.1515/hsz-2014-0127

Keywords for this article

antithrombin III; blood coagulation; heparin; Kallikrein; Kunitz inhibitor; lectin; thrombosis