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|Title:||Losartan and captopril treatment rescue normal thrombus formation in microfibril associated glycoprotein-1 (magp1) deficient mice|
Pereira, Danielle Sousa
Nery Diez, Ana Cláudia C.
Braga, Guilherme G.
Godoy, Juliana A.
Mendes, Camila B.
Santos, Leonardo dos
Krieger, José E.
Costa, Fábio 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|
|Subject:||Fator de crescimento transformador beta|
Metaloproteinases da matriz
|Appears in Collections:||IB - Artigos e Outros Documentos|
FCM - Artigos e Outros Documentos
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