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Study of the relationship between the level of plasma antioxidants and carotid intima-media thickness in a longitudinal study on Adult Health (ELSA-Brazil)

Grant number: 14/10161-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2014
Effective date (End): November 30, 2016
Field of knowledge:Biological Sciences - Biochemistry
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Flavia Carla Meotti
Grantee:Marli Stela Santana Maciel
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:11/18106-4 - Oxidation of uric acid by myeloperoxidase in inflammatory processes and the implications for cardiovascular disease, AP.JP

Abstract

Atherosclerosis is a chronic inflammatory disease, characterized by elevated oxidative stress in the vascular environment. Its diagnosis can be performed by measuring the mean carotid intima-media thickness by ultrasound. It is known that hyperuricemia is linked to the progression of cardiovascular disease (CVD). However, CVD is typically associated with a number of other factors and thereby the actual influence of uric acid is poorly established. Studies in our research group showed that in inflammatory environments, uric acid can be oxidized generating highly oxidizing compound, urate hydroperoxide and finally decompose allantoin. The production of these intermediates leads to oxidative imbalance in redox balance, oxidation of proteins involved in the activation of inflammatory cells and release of proinflammatory cytokines. Thus, a broad clinical investigation which correlates not only uric acid level, but their metabolism is very useful in understanding the biochemical mechanisms involved in the progression of CVD. Thus, this study will investigate the levels of uric acid, xanthine its precursor, its metabolite allantoin and enzymes involved in oxidative metabolism of uric acid, xanthine oxidase and myeloperoxidase in plasma of patients with swelling of the middle layer of the carotid intima-media. Furthermore, other antioxidants are researched, vitamin A (retinol) its precursor beta- carotene and its oxidized metabolite, retinoic acid. The rationale for simultaneous analysis of vitamin A and its derivatives is due to the positive relationship between this and the antioxidant uric acid in vascular disorders, as well as a likely direct effect of vitamin A on the metabolism of uric acid. The implementation of this project will only be possible through a partnership between our research group and Brazil ELSA program (Longitudinal Study of Adult Health), a multicenter cohort study, led by Prof. Paul Lotufo, from Center for Clinical and Epidemiological Research at USP, which trior 15.105 participants to assess cardiovascular risk. The purpose of ELSA is to investigate the incidence and risk factors for chronic diseases, especially cardiovascular and diabetes. From the implementation of this project, it is expected to label substances that may be informative for the development of CVD and assist effectively in prognoses, and filling gaps in existing information about the molecular mechanisms involved in the development of CVD. (AU)