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Ana Cristina Simões e Silvahttp://lattes.cnpq.br/4408599021040004Leonardo Cruz de Souzahttp://lattes.cnpq.br/3217952401500131Victor Teatini Ribeiro2021-09-30T21:11:54Z2021-09-30T21:11:54Z2021-07-27http://hdl.handle.net/1843/38218A Doença de Alzheimer (DA), principal causa de demência, desperta crescente interesse científico, uma vez que a sua fisiopatologia está, em grande parte, ainda por ser desvendada. O sistema-renina angiotensina (SRA) é um dos sistemas fisiológicos mais importantes para a homeostase. À medida que o conhecimento sobre as funções do SRA foi se acumulando, constatou-se a sua participação também em variados processos fisiopatológicos, incluindo as doenças psiquiátricas e neurodegenerativas. O envolvimento do SRA na fisiopatologia da DA, especificamente, ainda é pouco explorado. Este trabalho teve como principais objetivos: (1) realizar uma ampla revisão da literatura sobre o SRA, a DA e os possíveis pontos de interação entre ambos; (2) conduzir um estudo-piloto explorando o status do SRA em pacientes com DA e em indivíduos cognitivamente saudáveis, visando à geração de hipóteses fisiopatológicas. Para atender ao primeiro objetivo, realizamos pesquisa não sistemática nas bases PubMed/Medline e Google Acadêmico. Foram encontrados estudos originais pré-clínicos e clínicos que investigaram diretamente o papel do SRA na DA. Produzimos, então, um artigo de revisão narrativa com um sumário da evidência direta, acompanhada de uma discussão ampla sobre potenciais mecanismos. Para satisfazer ao segundo objetivo, conduzimos um estudo transversal, exploratório, de caso-controle, em que foram recrutados 14 pacientes com DA e 14 voluntários cognitivamente saudáveis da mesma faixa etária. De todos os participantes, obtivemos dados clínicos e neuropsicológicos, além de amostras de sangue e imagens por ressonância nuclear magnética (RNM) do encéfalo. Foram dosadas, no plasma, angiotensina II (Ang II) e angiotensina-(1-7) [Ang-(1-7)], as moléculas efetoras dos eixos clássico e alternativo do SRA, respectivamente. Constatou-se que a Ang-(1-7) está significativamente reduzida no plasma de indivíduos com DA. Nesse grupo, houve uma correlação positiva entre a Ang-(1-7) circulante e marcadores de lesão cerebrovascular na RNM. Nossos achados favorecem a tese de que o eixo alternativo do SRA está alterado na DA e indicam um possível mecanismo de interação. Os resultados fornecem subsídio para que estudos maiores, com poder estatístico adequado, testem essa hipótese.Alzheimer’s Disease (AD), the leading cause of dementia worldwide, is the subject of growing scientific interest, given that part of its pathophysiology is yet to be unveiled. The renin-angiotensin system (RAS) is one of the most important physiological systems for homeostasis. As the knowledge about the RAS and its functions has accumulated, the system has been implicated in many pathological processes as well, including psychiatric and neurodegenerative diseases. However, the RAS role in AD pathophysiology, in particular, remains largely unexplored. This study addressed this gap in knowledge by targeting two main objectives: (1) to perform a comprehensive literature review about the RAS, AD and their possible intersection points; (2) to conduct a pilot-study to explore the RAS status in AD patients compared to cognitively healthy individuals, so as to generate hypotheses. To accomplish the first goal, we have non-systematically searched throughout PubMed/Medline and Google Scholar databases. We have found pre-clinical and clinical primary studies which directly addressed RAS participation in AD. As a result, we have written a narrative review article that summarizes all direct pieces of evidence and discusses at length the potential mechanisms behind them. In order to achieve the second objective, we have conducted a cross-sectional, case-control exploratory study which recruited 14 patients with AD and 14 cognitively healthy age-matched volunteers. Clinical data, neuropsychological test results, blood samples and magnetic resonance imaging (MRI) were obtained from all participants. We have measured plasma levels of angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)], the effector peptides of RAS classical and alternative axis, respectively. Ang-(1-7) was found to be significantly reduced in AD patients. In the AD group, there was a positive correlation between circulating Ang-(1-7) and MRI markers of cerebrovascular lesions. Our findings strengthen the hypothesis that RAS alternative axis is downregulated in AD and points to a potential interaction mechanism. Moreover, these results provide a basis for conducting larger properly powered studies willing to test this hypothesis.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Medicina MolecularUFMGBrasilhttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessSistema Renina-AngiotensinaDoença de AlzheimerAngiotensinasDemênciaHomeostaseSistema Renina-AngiotensinaDoença de AlzheimerAngiotensina-(1-7)O Sistema Renina-Angiotensina na Doença de Alzheimer: revisão de literatura e estudo-pilotoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALO Sistema Renina-Angiotensina na Doença de Alzheimer Victor Teatini Ribeiro 2021 Versão final.pdfO Sistema Renina-Angiotensina na Doença de Alzheimer Victor Teatini Ribeiro 2021 Versão final.pdfapplication/pdf2551547https://repositorio.ufmg.br/bitstream/1843/38218/1/O%20Sistema%20Renina-Angiotensina%20na%20Doen%c3%a7a%20de%20Alzheimer%20Victor%20Teatini%20Ribeiro%202021%20Vers%c3%a3o%20final.pdfbfe39c3293a02a135eed7833019dc09fMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/38218/3/license.txtcda590c95a0b51b4d15f60c9642ca272MD53CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufmg.br/bitstream/1843/38218/2/license_rdfcfd6801dba008cb6adbd9838b81582abMD521843/382182021-09-30 18:11:54.74oai:repositorio.ufmg.br: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ório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2021-09-30T21:11:54Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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