ABC | Volume 114, Nº1, January 2019

Original Article Effects of Physical Training on the Myocardium of Oxariectomized LDLr Knockout Mice: MMP 2/9, Collagen I/III, Inflammation and Oxidative Stress Ledimar Brianezi, 1 Elisabete Ornelas, 1 Flávia de Sousa Gehrke, 2,3, 4 F ernando Luiz Affonso Fonseca, 4,5 Beatriz da Costa Aguiar Alves, 4 Luiz Vinicius de Alcantara Sousa, 4 Jessica Souza, 1 Laura Beatriz Mesiano Maifrino 1 Laboratório de Estudos Morfoquantitativo e Imunohistoquímico, Universidade São Judas Tadeu, 1 São Paulo, SP – Brazil Departamento de Farmácia, Universidade Paulista, 2 São Paulo, SP – Brazil Pós-Graduação em Ciências da Saúde, Hospital do Servidor Público Estadual, 3 São Paulo, SP – Brazil Laboratório de Análises Clínicas da Faculdade de Medicina do ABC, 4 Santo André, SP – Brazil Departamento de Ciências Farmacêuticas da Universidade Federal de São Paulo, 5 Diadema, SP – Brazil Mailing Address: Flávia de Sousa Gehrke • Universidade Paulista – Farmácia - R. Antônio Macedo, 505. Postal Code 03087-010, São Paulo, SP – Brazil E-mail: flaviagehrke@hotmail.com Manuscript received September 04, 2018, revised manuscript January 30, 2019, accepted March 10, 2019 DOI: 10.5935/abc.20190223 Abstract Background: The emergence of coronary heart disease is increased with menopause, physical inactivity and with dyslipidemia. Physical training is known to promote the improvement of cardiovascular functions. Objective: To investigate the effects of aerobic physical training on the left ventricle in ovariectomized LDL knockout mice. Methods: Thirty animals were divided into 6 groups (n = 5): Sedentary non-ovariectomized control; Sedentary ovariectomized control; Trained ovariectomized control; Sedentary non-ovariectomized LDL-knockout, sedentary ovariectomized LDL‑knockout and trained ovariectomized LDL‑knockout. We analyzed the average parameters of apparent density of collagen fibers types I and III, and metalloproteinase type 2 and type 9, were considered significant p < 0.05. Results: The results showed that the proposed exercise protocol altered the volume of type I collagen fibers, altered collagen remodeling parameters (MMP-2), and also reduced the 8-hydroxy-2’-deoxyguanosine (8OHdG) oxidative stress parameter. Conclusion: Moderate intensity aerobic training acts on collagen fiber volume, on collagen remodeling with the reduction of oxidative stress in the left ventricles of ovariectomized LDL-knockout mice. (Arq Bras Cardiol. 2020; 114(1):100-105) Keywords: Coronary Artery Disease; Exercise; Menopause; Dyslipidemias; Motor Activity; Collagen; Oxidative Stress; Inflammation; Mice. Introduction During the aging process, menopausal women are at increased risk of developing conditions such as dyslipidemia, hypertension, insulin resistance and changes in body composition, where lifestyle and sedentarism are associated with a higher prevalence of the development of cardiovascular disease (CD). 1,2 The aging process is associated with increased oxidative stress resulting in damage of several cell macromolecules, partly due to decreased antioxidant capacity as well as reduced repair capacity, resulting in increased susceptibility to apoptosis. 3,4 Particularly in menopausal women, neuroendocrine alterations affect the functionality, metabolic capacity and antioxidant activity of numerous organs, especially due to the lack of estrogen, considered a female antioxidant, resulting in an additional increase of oxidative stress. 5 Lipid metabolism is also influenced by physiological changes during menopause resulting in an increase in LDL and a decrease in HDL and contributes to the emergence of cardiovascular diseases. 6,7 When compared to men of the same age, postmenopausal women are at an increased risk of developing heart disease. 8,9 It is one of the main causes of morbidity and mortality in this physiological stage. 10 Regular physical activity relieves the effects of aging and menopauseand improves aerobic fitness,maintainingbodyweight index of visceral fat, plasma lipid levels, increased insulin sensitivity, increased baroreflex sensitivity and improved endothelial function, capillary wall shear stress which results in increased blood flow, stimulating nitric oxide release. 11-13 These factors promote a better health-related quality of life and prolong survival and can be considered essential non‑pharmacological standards in the treatment of postmenopausal effects and other physiological and pathological conditions. 14,15 The objective of this study is to analyze the effects of aerobic physical training on the left ventricle in ovariectomized wildtype and LDLr knockout female mice on the following 100

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