Evaluation of the role of fibrillin-1 in arterial thrombosis

Author(s)

Ana Cláudia Coelho Nery Diez

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2013-07-06

Examining board members

Claudio Chrysostomo Werneck; Edson Rosa Pimentel; Marcelo Brocchi; Robson de Queiroz Monteiro; Maria Luiza Vilela Oliva

• Advisor: Claudio Chrysostomo Werneck

Abstract

Recent works show that an increased activation of the TGF-? is associated with most of the symptoms of the Marfan syndrome. Studies using mouse models of Marfan treated with losartan have been shown to prevent the degradation of the elastic matrix. Other investigators suggest that the metalloproteinases and the noncanonical ERK signaling are involved in the breakdown of the elastic fiber, which results in the aneurysm. In this study we investigated the role of fibrillin-1 in the arterial thrombosis model using mouse models of Marfan. We analyzed thrombus formation, platelet levels, APTT, PT and TT time, hemodynamic parameter, TGF-? levels, MMP activity as well as platelets, elastic fibers morphology and thrombus. This study demonstrated that Fbn1mg?/+ mice take about 120±21,07 minutes for the thrombus to be formed when compared with wild type, 58±7,16. When these Fbn1mg?/+ mice were treated with antihypertensive losartan and captopril the time taken for the thrombus formation was reduced in 57,5% and 67,5%, respectively. The activity of metalloproteinases and activity TGF-? was increased in the Fbn1mg?/+, however no significant difference between the hemodynamic parameters, levels of totals TGF-?, morphological platelets, elastic fiber and thrombus were observed. Finally, the results suggested that fibrillin-1 interferes with this process and antihypertensive affect the physiology of Fbn1mg?/+ mice. This study suggested that somehow drugs interfere with elastic matrix remodeling due to a decrease in the activity of matrix metalloproteinases which results in the recovery time of thrombus formation (AU)

• FAPESP's process: 09/03058-4 - Evaluation of fibrillina-1 role in arterial thrombogenesis
• Grantee: Ana Cláudia Coelho Nery Diez
• Support Opportunities: Scholarships in Brazil - Doctorate