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Participation B2R bradykinin receptor in phenotypic improvement induced by Ramipril in a murine model for Marfan Syndrome

Grant number: 13/20363-0
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2014
Effective date (End): July 31, 2016
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Lygia da Veiga Pereira
Grantee:Elisa Ito Kawahara
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Marfan Syndrome (MFS) is an autosomal dominant disease that affects the connective tissue. Has an incidence of 1 per 5000 individuals. The main clinical manifestations are progressive dilation and rupture of the aorta, bone overgrowth, scoliosis, chest deformities and retinal detachment. The MFS is caused by mutations in the FBN1 gene, that encodes the extracellular protein fibrillin-1, major component of microfibrils, which form the elastic fibers. Studies have shown that mutations in the fibrillin-1 gene leads to an indiscriminate increase in active TGF-² in the matrix, which results in major phenotypes of the disease. The main product of the Renin-Angiotensin System (RAS) is the Angiotensin II (Ang-II), involved in the regulation of bone mass and activity of TGF-². Therapeutic strategies using drugs that act on the RAS have been targets of studies in animal models. Ramipril, inhibitor of ACE (angiotensin-converting enzyme), tested in the animal model for MFS mg”loxPneo from our laboratory showed a significant increase of 35% in Fbn1 gene transcription and a phenotypic improvement of the MFS, including bone phenotype. Its mechanism of action is not completely elucidated, and may act by decreasing the production of Ang-II and subsequent decrease in the levels of TGF-², or by inhibiting the degradation of bradykinin, that acts through receptors B1R and B2R by Ang II. The bradykinin B2R directly activates its receptor, which induces physiological actions opposite to those of Ang-II. The objective of this work is to evaluate the role of bradykinin receptor B2R in the therapeutic effect of Ramipril bone phenotype in animal model mg”loxPneo for Marfan Syndrome.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
KAWAHARA, Elisa Ito. Characterization of the skeletal phenotype of the mg?loxPneo mouse model of Marfan syndrome and analysis of the mechanisms of pathogenesis. 2016. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.

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