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      Atorvastatina Atenua o Remodelamento Vascular em Camundongos com Síndrome Metabólica

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          Resumo

          Fundamento

          A síndrome metabólica é caracterizada por um conjunto de comorbidades. Durante a síndrome, observam-se alterações estruturais no sistema cardiovascular, especialmente o remodelamento vascular. Uma das causas predisponentes para essas alterações é a inflamação crônica oriunda de mudanças na estrutura e composição do tecido adiposo perivascular. Atorvastatina é eficaz no tratamento das dislipidemias. No entanto, seus efeitos pleiotrópicos não são totalmente compreendidos. Supõe-se que, durante a síndrome metabólica, ocorre remodelamento vascular e que o tratamento com atorvastatina pode ser capaz de atenuar tal condição.

          Objetivos

          Avaliar os efeitos do tratamento com atorvastatina sobre o remodelamento vascular em modelo experimental de síndrome metabólica.

          Métodos

          Camundongos Swiss receberam dieta controle ou dieta hiperglicídica por 18 semanas. Após 14 semanas de dieta, os camundongos foram tratados com veículo ou atorvastatina (20mg/kg) durante 4 semanas. Foram avaliados o perfil nutricional e metabólico por testes bioquímicos; análise estrutural da artéria aorta por histologia e dosagem de citocinas por ensaio imunoenzimático. O nível de significância aceitável para os resultados foi p <0,05.

          Resultados

          A dieta hiperglicídica promoveu o desenvolvimento de síndrome metabólica. Tal fato culminou no remodelamento hipertrófico do músculo liso vascular e tecido adiposo perivascular. Além disso, houve aumentos das citocinas TNF-α e IL-6 circulantes e no tecido adiposo perivascular. O tratamento com atorvastatina reduziu significativamente os danos metabólicos, o remodelamento vascular e os níveis de citocinas.

          Conclusão

          Atorvastatina ameniza danos metabólicos associados à síndrome metabólica induzida por dieta hiperglicídica, além de atenuar o remodelamento vascular, sendo esses efeitos associados à redução de citocinas pró-inflamatórias.

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          Most cited references68

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          Relation of body fat distribution to metabolic complications of obesity.

          The importance of body fat distribution as a predictor of metabolic aberrations was evaluated in 9 nonobese and 25 obese, apparently healthy women. Plasma glucose and insulin levels during oral glucose loading were significantly higher in women with predominantly upper body segment obesity than in women with lower body segment obesity. Of the former group, 10 of 16 subjects had diabetic glucose tolerance results, while none of the latter group was diabetic. Fasting plasma triglyceride levels were also significantly higher in the upper body segment obese women. The site of adiposity in the upper body segment obese women was comprised of large fat cells, while in the lower body segment obese subjects, it was formed of normal size cells. In both types of obesity, abdominal fat cell size correlated significantly with postprandial plasma glucose and insulin levels. Thigh fat cell size gave no indication as to the presence of metabolic complications. Thigh adipocytes were also resistant to epinephrine-stimulated lipolysis, presumably due to an increase in alpha-adrenergic receptors. Thus, in women, the sites of fat predominance offer an important prognostic marker for glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. This association may be related to the disparate morphology and metabolic behavior of fat cells associated with different body fat distributions.
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            Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome

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              Adipose tissue as an endocrine organ.

              Obesity is characterized by increased storage of fatty acids in an expanded adipose tissue mass and is closely associated with the development of insulin resistance in peripheral tissues such as skeletal muscle and the liver. In addition to being the largest source of fuel in the body, adipose tissue and resident macrophages are also the source of a number of secreted proteins. Cloning of the obese gene and the identification of its product, leptin, was one of the first discoveries of an adipocyte-derived signaling molecule and established an important role for adipose tissue as an endocrine organ. Since then, leptin has been found to have a profound role in the regulation of whole-body metabolism by stimulating energy expenditure, inhibiting food intake and restoring euglycemia, however, in most cases of obesity leptin resistance limits its biological efficacy. In contrast to leptin, adiponectin secretion is often diminished in obesity. Adiponectin acts to increase insulin sensitivity, fatty acid oxidation, as well as energy expenditure and reduces the production of glucose by the liver. Resistin and retinol binding protein-4 are less well described. Their expression levels are positively correlated with adiposity and they are both implicated in the development of insulin resistance. More recently it has been acknowledged that macrophages are an important part of the secretory function of adipose tissue and the main source of inflammatory cyokines, such as TNFalpha and IL-6. An increase in circulating levels of these macrophage-derived factors in obesity leads to a chronic low-grade inflammatory state that has been linked to the development of insulin resistance and diabetes. These proteins commonly known as adipokines are central to the dynamic control of energy metabolism, communicating the nutrient status of the organism with the tissues responsible for controlling both energy intake and expenditure as well as insulin sensitivity. 2009 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Journal
                Arq Bras Cardiol
                Arq Bras Cardiol
                abc
                Arquivos Brasileiros de Cardiologia
                Sociedade Brasileira de Cardiologia - SBC
                0066-782X
                1678-4170
                10 June 2021
                October 2021
                : 117
                : 4
                : 737-747
                Affiliations
                [1 ] orgnameUniversidade Federal de Jataí orgdiv1Unidade Acadêmica de Ciências da Saúde Jataí GO Brasil originalUniversidade Federal de Jataí - Unidade Acadêmica de Ciências da Saúde, Jataí, GO - Brasil
                [2 ] orgdiv1Faculdade de Medicina de Ribeirão Preto orgnameUniversidade de São Paulo orgdiv2Departamento de Farmacologia Ribeirão Preto SP Brasil originalFaculdade de Medicina de Ribeirão Preto, Universidade de São Paulo - Departamento de Farmacologia, Ribeirão Preto, SP - Brasil
                [1 ] Brazil originalUniversidade Federal de Jataí - Unidade Acadêmica de Ciências da Saúde, Jataí, GO - Brazil
                [2 ] Brazil originalFaculdade de Medicina de Ribeirão Preto, Universidade de São Paulo - Departamento de Farmacologia, Ribeirão Preto, SP - Brazil
                Author notes
                Correspondência: Rafael Menezes da Costa • Universidade Federal de Jataí - Unidade Acadêmica de Ciências da Saúde - BR 364, km 195, 3800. CEP 75801-615, Jataí, GO – Brasil E-mail: rafael.menezess@ 123456yahoo.com.br

                Contribuição dos autores

                Concepção e desenho da pesquisa, Revisão crítica do manuscrito quanto ao conteúdo intelectual importante, Análise estatística e Redação do manuscrito: Carvalho KFS, Costa RM; Obtenção de dados: Carvalho KFS, Ferreira AAM, Barbosa NC, Alves JV; Análise e interpretação dos dados: Carvalho KFS, Ferreira AAM, Barbosa NC, Alves JV, Costa RM; Obtenção de financiamento: Costa RM.

                Potencial conflito de interesse

                Não há conflito com o presente artigo

                Mailing address: Rafael Menezes da Costa • Universidade Federal de Jataí - Unidade Acadêmica de Ciências da Saúde - BR 364, km 195, 3800. Postal Code 75801-615, Jataí, GO – Brazil E-mail: rafael.menezess@yahoo.com.br

                Author Contributions

                Conception and design of the research, Statistical analysis, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Carvalho KFS, Costa RM; Acquisition of data: Carvalho KFS, Ferreira AAM, Barbosa NC, Alves JV; Analysis and interpretation of the data: Carvalho KFS, Ferreira AAM, Barbosa NC, Alves JV, Costa RM; Obtaining financing: Costa RM.

                Potential Conflict of Interest

                No potential conflict of interest relevant to this article was reported.

                Author information
                https://orcid.org/0000-0002-5174-5710
                Article
                abc.20200322
                10.36660/abc.20200322
                8528348
                34161419
                117b6e8a-78f1-4067-bbd9-50ef2415f4d8

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 April 2020
                : 14 September 2020
                : 04 November 2020
                Page count
                Figures: 12, Tables: 2, Equations: 0, References: 61
                Funding
                Funded by: CNPq
                Award ID: 433898/2018-06
                Fontes de financiamento O presente estudo foi financiado pelo CNPq (Processo 433898/2018-06)
                Categories
                Artigo Original

                dislipidemias,carbohidratos da dieta,síndrome metabólica,remodelamento vascular,atorvastatina,inflamação,camundongo

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