The impairment of plasma kallikrein action on homeostasis by kallikrein inhibitor comprising RGD sequence established a novel target in antithrombotic therapies

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Autor(es): dc.contributorUniversidade Federal de São Paulo (UNIFESP)-
Autor(es): dc.contributorUniversidade Estadual de Minas Gerais-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorMedina, A. F.-
Autor(es): dc.creatorSalu, B. R.-
Autor(es): dc.creatorde Brito, M. V.-
Autor(es): dc.creatorBonturi, C. R.-
Autor(es): dc.creatorMeneghetti, M. C.Z.-
Autor(es): dc.creatorMaffei, F. H.A.-
Autor(es): dc.creatorOliva, M. L.V.-
Data de aceite: dc.date.accessioned2025-08-21T19:59:57Z-
Data de disponibilização: dc.date.available2025-08-21T19:59:57Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-10-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.procbio.2022.08.013-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/241545-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/241545-
Descrição: dc.descriptionCoagulation contact pathway inhibitors have aroused interest in the treatment and prevention of thrombosis due to their lower hemorrhagic effects. We investigate the recombinant kallikrein inhibitor (rBbKIm) containing the RGD/RGE motif and its related peptides in arterial thrombosis models. rBbKIm prolonged activated partial thromboplastin time by 3.5 (8.6 µM) and 4.1 times (17.2 µM), and extended the arterial occlusion time in a dose-dependent manner: 2.0 mg/kg (48.83 ± 15.87 min), 4.0 mg/kg (73.06 ± 21.38 min) and 8.0 mg/kg (94.13 ± 11.25 min) compared with control (0.15 M NaCl, 29.70 ± 7.14 min). Similar results were obtained with the RGD-peptide, 2.5 mg/kg (62.85 ± 18.53 min) and 5.0 mg/kg (89.50 ± 8.63 min). Thrombus sizes were decreased in the rBbKIm, RGD-peptide, and fondaparinux (0.7 mg/kg) treated groups, due to reduced adhesion of platelet to the endothelium. ADP-induced platelet aggregation ex vivo was inhibited by both rBbKIm (4.0 mg/kg, 75 %) and the RGD-peptide (5.0 mg/kg, 56 %), and they did not modify the bleeding time in contrast to fondaparinux. rBbKIm and RGD-related-peptide delayed the artery occlusion and reduced the thrombus size without any modification of the bleeding time, thereby impairing the aggregation and/or adhesion of platelets, making them useful for thrombosis therapy.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionDepartment of Biochemistry and Molecular Biology Universidade Federal de São Paulo, SP-
Descrição: dc.descriptionDepartment of Molecular Biology Universidade Estadual de Minas Gerais, Minas Gerais-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics Universidade Estadual Paulista, São Paulo-
Descrição: dc.descriptionDepartment of Surgery and Orthopedics Universidade Estadual Paulista, São Paulo-
Formato: dc.format1-12-
Idioma: dc.languageen-
Relação: dc.relationProcess Biochemistry-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectArterial thrombosis-
Palavras-chave: dc.subjectBlood coagulation-
Palavras-chave: dc.subjectIntegrin-
Palavras-chave: dc.subjectKallikrein-
Palavras-chave: dc.subjectPlatelets-
Título: dc.titleThe impairment of plasma kallikrein action on homeostasis by kallikrein inhibitor comprising RGD sequence established a novel target in antithrombotic therapies-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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