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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Improving the understanding of plasma kallikrein contribution to arterial thrombus formation using two plant protease inhibitors

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Autor(es):
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Salu, Bruno R. [1] ; Pando, Silvana Cristina [1, 2] ; De Brito, V, Marlon ; Medina, Andre Fernando [3] ; Odei-Addo, Frank [4] ; Frost, Carminita [4] ; Naude, Ryno [4] ; Sampaio, Misako U. [3] ; Emsley, Jonas [5] ; Maffei, Francisco Humberto A. [6] ; Oliva, V, Maria Luiza
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] V, Univ Fed Sao Paulo, Dept Biochem, Rua Tres de Maio 100, BR-04044020 Sao Paulo, SP - Brazil
[2] Univ Fed Amazonas, Dept Physiol Sci, ICB, Manaus, Amazonas - Brazil
[3] De Brito, Marlon, V, V, Univ Fed Sao Paulo, Dept Biochem, Rua Tres de Maio 100, BR-04044020 Sao Paulo, SP - Brazil
[4] Nelson Mandela Univ, Dept Biochem & Microbiol, Port Elizabeth - South Africa
[5] Univ Nottingham, Ctr Biomol Sci, Sch Pharm, Nottingham - England
[6] Sao Paulo State Univ, Dept Surg & Orthoped, Botucatu, SP - Brazil
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: PLATELETS; v. 30, n. 3, p. 305-313, APR 3 2019.
Citações Web of Science: 0
Resumo

The purpose of antithrombotic therapy is the prevention of thrombus formation and/or its extension with a minimum risk of bleeding. The inhibition of a variety of proteolytic processes, particularly those of the coagulation cascade, has been reported as a property of plant protease inhibitors. The role of trypsin inhibitors (TIs) from Delonix regia (Dr) and Acacia schweinfurthii (As), members of the Kunitz family of protease inhibitors, was investigated on blood coagulation, platelet aggregation, and thrombus formation. Different from Acacia schweinfurthii trypsin inhibitor (AsTI), Delonix regia trypsin inhibitor (DrTI) is a potent inhibitor of FXIa with a K-iapp of 1.3 x 10(-9) M. In vitro, both inhibitors at 100 mu g corresponding to the concentrations of 21 mu M and 15.4 mu M of DrTI and AsTI, respectively, increased approximately 2.0 times the activated partial thromboplastin time (aPTT) in human plasma compared to the control, likely due to the inhibition of human plasma kallikrein (huPK) or activated factor XI (FXIa), in the case of DrTI. Investigating in vivo models of arterial thrombus formation and bleeding time, DrTI and AsTI, 1.3 mu M and 0.96 mu M, respectively, prolonged approximately 50% the time for total carotid artery occlusion in mice compared to the control. In contrast to heparin, the bleeding time in mice treated with the two inhibitors did not differ from that of the control group. DrTI and AsTI inhibited 49.3% and 63.8%, respectively, ex vivo murine platelet aggregation induced by adenosine diphosphate (ADP), indicating that these protein inhibitors prevent arterial thrombus formation possibly by interfering with the plasma kallikrein (PK) proteolytic action on the intrinsic coagulation pathway and its ability to enhance the platelet aggregation activity on the intravascular compartment leading to the improvement of a thrombus. (AU)

Processo FAPESP: 17/06630-7 - Fragmentos derivados de proteínas com seletividade para inibição de enzimas de mamíferos e micro-organismos e seu papel como agente anti-inflamatório, antimicrobiano, antitrombótico e antitumoral: mecanismo de ação
Beneficiário:Maria Luiza Vilela Oliva
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 17/07972-9 - Desenvolvimento de compostos para profilaxia e tratamento de doenças cardiovasculares
Beneficiário:Maria Luiza Vilela Oliva
Linha de fomento: Auxílio à Pesquisa - Regular