ABC | Volume 112, Nº2, February 2019

Original Article Evaluation of Collagen Fibers, MMP2, MMP9, 8-OHdG and Apoptosis in the Aorta of Ovariectomized LDL Knockout Mice Submitted to Aerobic Exercise Laura Beatriz M. Maifrino, 1 Nathalia E. A. de Lima, 1 Mara R. Marques, 2 Clever G. Cardoso, 2 Lidiane B. de Souza, 3 Tabata de Carvalho Tomé, 3 Hananiah Tardivo Quintana, 3 Flavia de Oliveira, 3 Beatriz da Costa Aguiar Alves Reis, 4 Fernando Luiz Affonso Fonseca 4 Universidade São Judas Tadeu, 1 São Paulo, SP – Brazil Universidade Federal de Goiás, 2 Goiânia, GO – Brazil Departamento de Biociências da Universidade Federal de São Paulo, 3 São Paulo, SP – Brazil Faculdade de Medicina do ABC, 4 Santo André, SP – Brazil Mailing Address: Beatriz da Costa Aguiar Alves Reis • Av. Príncipe de Gales, 821. Postal Code 09060-650, Santo André, SP – Brazil E-mail: bcaalves@uol.com.br Manuscript received December 09, 2017, revised manuscript May 04, 2018, accepted July 23, 2018 DOI: 10.5935/abc.20180263 Abstract Background: In menopause, there is greater cellular exposure to oxidative stress, related to the decreased antioxidative effects of estrogen. These metabolic changes favor the progression of cardiovascular diseases, such as atherosclerosis. Abnormal function of the aorta - the most important artery - is associated with many cardiovascular diseases. Collagen, especially types I and III, is one of the most important aortic wall components and it can be affected by many factors, including menopause. The 8-OHdG is one of the main markers of DNA oxidative damage induced by reactive oxygen species (ROS). Objective: We aimed to investigate effects of moderate aerobic training on the ascending aorta of LDL-knockout (LDL-KO) and ovariectomized female mice. Methods: A total of 15 C57BL/6 mice and 15 LDL-KO mice were divided into experimental groups. The thickness and volume density of types I and III collagen fibers were performed by morphoquantitative analysis, whereas the MMP-2 and MMP-9 and 8-OHdG were detected by immunohistochemistry and apoptosis was detected by the TUNEL assay. The significance level for all tests was p < 0.05. Results: Exercise causes an increase in the thickness of the aorta in LDL-KO groups, particularly accentuated in the ovariectomized groups. The type I collagen fibers showed an increase in volume density influenced by training in both Control groups and in the LDL-KO group. Type III collagen density decreased in both groups. The MMP-2 showed moderade immunostaining in the tunica media in LDL-KO groups, which did not occur in the control groups and the MMP-9 stained irregularly in all tissues. The marker 8-OhdG was stronger in the exercise training groups. Additionally, the ovariectomy, the exercise training and the LDL-KO treatments increased apoptosis. Conclusion: These results suggest that moderate-intensity aerobic exercise in ovariectomized mice associated to an increase in LDL rate possibly increases oxidative stress and apoptosis induction. (Arq Bras Cardiol. 2019; 112(2):180-188) Keywords: Rats; Cardiovascuar Diseases; Menopause; Fibrillar Collagens/analysis; Ovariectomy; Exercise; Cholesterol, LDL. Introduction Menopause is a period during which women suffer changes in metabolic profile due to decreased production of hormones such as estrogen. 1-3 These metabolic changes favor the progression of cardiovascular diseases, such as atherosclerosis. 4 Abnormal function of the aorta - the most important artery - is associated with many cardiovascular diseases. Collagen, especially types I and III, is one of the most important aortic wall components and it can be affected by many factors, including menopause. 5 Physical exercises are recommended for preventing c a r d i o v a s c u l a r d i s e a s e s du r i n g menop a u s e . 6,7 However, moderate-to-high intensity physical activity causes increased oxidative stress in cells and tissues, raising the risk of cardiovascular disease. 8-10 The adaptation of the body to oxidative stress may be impaired in individuals with low levels of estrogen, which binds to specific cellular receptors and accelerate the production of various antioxidants by cells. Little is known about the effects of physical activity on the development of atherosclerosis and metabolic changes that are characteristic of menopause. Relevant data for the elucidation of these effects have been obtained with the use of markers such as 8-hydroxydeoxyguanosine (8‑OHdG), metalloproteinases (MMPs), apoptosis detection and quantification of collagen types III and I. 180