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Type: Artigo
Title: Losartan And Captopril Treatment Rescue Normal Thrombus Formation In Microfibril Associated Glycoprotein-1 (magp1) Deficient Mice
Author: Vassequi-Silva
Tallita; Pereira
Danielle Sousa; Nery Diez
Ana Claudia C.; Braga
Guilherme G.; Godoy
Juliana A.; Mendes
Camila B.; dos Santos
Leonardo; Krieger
Jose E.; Antunes
Edson; Costa
Fabio T. M.; Vicente
Cristina P.; Werneck
Claudio C.
Abstract: MAGP1 is a glycoprotein present in the elastic fibers and is a part of the microfibrils components. MAGP1 interacts with von Willebrand factor and the active form of TGF-beta and BMP. In mice lacking MAGP1, thrombus formation is delayed, increasing the occlusion time of carotid artery despite presenting normal blood coagulation in vitro. MAGP1-containing microfibrils may play a role in hemostasis and thrombosis. In this work, we evaluated the function of MAGP1 and its relation to TGF-beta in the arterial thrombosis process. Methods and results: We analyzed thrombus formation time in wild type and MAGP1-deficient mice comparing Rose Bengal and Ferric Chloride induced arterial lesion. The potential participation of TGF-beta in this process was accessed when we treated both wild type and MAGP1-deficient mice with losartan (an antihypertensive drug that decreases TGF-beta activity) or captopril (an angiotensin converting enzyme inhibitor that was used as a control antihypertensive drug). Besides, we evaluated thrombus embolization and the gelatinolytic activity in the arterial walls in vitro and ex vivo. Losartan and captopril were able to recover the thrombus formation time without changing blood pressure, activated partial thromboplastin time (aPTT), PT (prothrombin time), platelet aggregation and adhesion, but decreased gelatinase activity. Conclusions: Our results suggest that both treatments are effective in the prevention of the sub-endothelial ECM degradation, allowing the recovery of normal thrombus formation. (C) 2015 Elsevier Ltd. All rights reserved.
Subject: Microfibril-associated Glycoprotein
Arterial Thrombosis
Transforming Growth Factor-beta
Antihypertensive Drugs
Extracellular Matrix
Matrix Metalloproteinases
Editor: Pergamon-Elsevier Science LTD
Rights: fechado
Identifier DOI: 10.1016/j.thromres.2015.12.004
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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