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Evaluation of MAGP1 function in neointima formation

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Author(s):
Tallita Vassequi Silva
Total Authors: 1
Document type: Master's Dissertation
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
Defense date:
Examining board members:
Claudio Chrysostomo Werneck; Jose Camillo Novello; Wilson Nadruz Junior
Advisor: Claudio Chrysostomo Werneck
Abstract

Elastic fibers are responsible for providing support to tissues such as aorta, skin and lung. They are composed of two distinct components, elastin and microfibrils, when analyzed by electron microscopy. Previously, researchers believed that the main function of the microfibrils network, mainly composed of fibrilin and MAGPs, was the formation of the elastic fiber. But, today, we know that the microfibril network is essential for molecular signaling also. The MAGPs are proteins apparently important for the structural functions of the microfibrils and development. Although its biological function is not known yet, many studies have demonstrated its interaction with various molecules in vitro, such as fibrilin 1 and 2, tropoelastin, biglycan, decorin and type VI collagen. So far no pathology was related to MAGP1 deficiency or mutations. However, preliminary data show that MAGP1 deficient mice when assayed using angioplasty model they developed more neointima than wild-type animals. The angioplasty procedure often results in vascular remodeling, leading to restenosis. Many studies have shown that TGF-ß is related to this process mainly because this growth factor is able to modulate the development and vascular remodeling. Take into account recent data showing that MAGP1 has the ability to interact with active TGF-ß, it was our interest to treat the MAGP1 deficient and wild-type mice with losartan (antagonist of TGF-ß) to verify the MAGP1 function and possible involvement of TGF-? in the neointima formation. Mice were treated with losartan or placebo for 4 weeks and then tested on angioplasty, blood pressure measurement and serum TGF-ß. It was observed that all animals are normotensive, and that losartan treatment resulted in a neointima reduction compared with untreated animals. No difference in neointima formation was observed between the MAGP1 deficient and wild-type mice. There was no change in total serum TGF-ß levels. Data suggest that MAGP1, apparently is not important in neointima formation and the losartan treatment is effective in reducing neointima formation without affecting blood pressure and levels of TGF-ß (AU)

FAPESP's process: 09/03495-5 - Evaluation MAGP-1's function in neointimal formation.
Grantee:Tallita Vassequi da Silva
Support Opportunities: Scholarships in Brazil - Master