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- Title
Cardioprotection Generated by Aerobic Exercise Training is Not Related to the Proliferation of Cardiomyocytes and Angiotensin-(1-7) Levels in the Hearts of Rats with Supravalvar Aortic Stenosis.
- Authors
Ferreira Mota, Gustavo Augusto; Borges de Souza, Sérgio Luiz; Loureiro da Silva, Vitor; Gatto, Mariana; Salomé de Campos, Dijon Henrique; Sant’Ana, Paula Grippa; Fernandes Vileigas, Danielle; Padovani, Carlos Roberto; Casarini, Dulce Elena; Menezes de Oliveira, Edilamar; Zanati Bazan, Silméia Garcia; Fernandes, Tiago; Mateus Sugizaki, Mario; Ricardo de Morais Gomes, Enéas; Carlos Cicogn, Antonio
- Abstract
Background/Aims: The beneficial effect of aerobic exercise training (ET) on cardiac remodeling caused by supravalvar aortic stenosis (AS) has been demonstrated in experimental studies; however, the mechanisms responsible for improving cardiac function are not entirely under-stood. We evaluated whether ET-generated cardioprotection in pressure-overloaded rats is dependent on cardiomyocyte proliferation, increased angiotensin-(1-7) (Ang-1-7) levels, and its receptor in the myocardium. Methods: Eighteen weeks after ascending AS surgery, Wistar rats were randomly assigned to four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary aortic stenosis (AS-Sed) and exercised aortic stenosis (AS-Ex) groups. The moderate treadmill exercise protocol was performed for ten weeks. The functional capacity was assessed by treadmill exercise testing. Cardiac structure and function were evaluated by echocardiogram. Cardiomyocyte proliferation was evaluated by flow cytometry. Expression of cell cycle regulatory genes as CCND2, AURKB, CDK1, and MEIS1 was verified by RT-qPCR. Cardiac and plasma angiotensin I (Ang I), angiotensin II (Ang II), and Ang-(1-7) levels were analyzed by high-performance liquid chromatography (HPLC). The angiotensin-converting enzyme (ACE) activity was assessed by the fluorometric method and protein expression of AT1 and Mas re-ceptors by Western blot. Results: The AS-Ex group showed reduced left ventricular wall rela-tive thickness and improved ejection fraction; also, it showed decreased gene expression of myocyte cell cycle regulators, ACE, Ang I, Ang II and Ang II/Ang-(1-7) ratio levels compared to AS-Sed group. However, ET did not induce alterations in Ang-(1-7) and cardiac Mas receptor expression and myocyte proliferation. Conclusion: Aerobic exercise training improves systolic function regardless of myocyte proliferation and Ang-(1-7)/Mas receptor levels. However, the ET negatively modulates the vasoconstrictor/hypertrophic axis (ACE/Ang II) and decreases the expression of negative regulatory genes of the cell cycle in cardiomyocytes of rats with supravalvular aortic stenosis.
- Publication
Cellular Physiology & Biochemistry (Cell Physiol Biochem Press GmbH & Co. KG), 2020, Vol 54, Issue 4, p719
- ISSN
1015-8987
- Publication type
Article
- DOI
10.33594/000000251