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Evaluation of fibrillina-1 role in arterial thrombogenesis

Grant number: 09/03058-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2009
Effective date (End): June 30, 2013
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Claudio Chrysostomo Werneck
Grantee:Ana Cláudia Coelho Nery Diez
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Mutations in the gene of fibrillin-1, present in the elastic fiber, are related to the Marfan syndrome, a dominant autosomic genetic disease, characterized by a disorder in the connective tissue. Carriers of this syndrome frequently exhibit anomalies in skeletal, pulmonary, cardic, ocular, and vessel structures, among others. The majority of its symptoms are likely related to a hyper-activation of the TGF-beta factor, due to a reduction in the amount of fibillin-1 in the extracellular matrix. Papers that have been carried out support to this hypothesis, by showing that syndrome carriers, when treated with the pharmaceutical compound losartan, present a significant improvement in clinical signals, due to a reduction in the level of TGF-beta. Data of our group demonstrate the importance of microfibrils components in the formation process of the arterial thrombus. Mice wich are deficient in MAGP-1 require almost double the time of wild mice to have the thrombus formed. Preliminary data suggest that the ones deficient in fibrillin-1 also present the same problem. Thus, the central objective of this project is to achieve a better understanding of the function of fibrillin-1 in the process of arterial thrombosis. Therefore, considering the possible influence of TGF-beta, we intend treat mice that are wild and deficient in fibrillin-1 with and without losartan, to carry out the thrombosis arterial experiment. We will then analyze the levels of arterial in the plasma and platelets of the animals. We also intend to perform a proteomic analysis, so as to compare the content of the platelet obtained, given that its granules store important molecules which contribute to the formation of thrombosis.

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
DIEZ, Ana Cláudia Coelho Nery. Evaluation of the role of fibrillin-1 in arterial thrombosis. 2013. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia.

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