Department of Internal Medicine, Botucatu Medical School, São Paulo State University, Botucatu, São Paulo, Brazil.
Department of Biostatistics, Institute of Bioscience, São Paulo State University, Botucatu, São Paulo, Brazil.
Cell Physiol Biochem. 2020 Jul 31;54(4):719-735. doi: 10.33594/000000251.
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 understood. 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.
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 receptors by Western blot.
The AS-Ex group showed reduced left ventricular wall relative 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.
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.
背景/目的：已有实验研究证明，有氧运动训练（ET）对瓣上型主动脉狭窄（AS）引起的心脏重构具有有益作用；然而，改善心脏功能的机制尚不完全清楚。我们评估了压力超负荷大鼠中 ET 产生的心脏保护作用是否依赖于心肌细胞增殖、血管紧张素-（1-7）（Ang-1-7）水平升高及其在心肌中的受体。
在升主动脉 AS 手术后 18 周，Wistar 大鼠被随机分为四组：安静对照组（C-Sed）、运动对照组（C-Ex）、安静主动脉狭窄组（AS-Sed）和运动主动脉狭窄组（AS-Ex）。进行为期 10 周的中等强度跑步机运动方案。通过跑步机运动测试评估功能能力。通过超声心动图评估心脏结构和功能。通过流式细胞术评估心肌细胞增殖。通过 RT-qPCR 验证细胞周期调节基因 CCND2、AURKB、CDK1 和 MEIS1 的表达。通过高效液相色谱法（HPLC）分析心脏和血浆中的血管紧张素 I（Ang I）、血管紧张素 II（Ang II）和 Ang-（1-7）水平。通过荧光法评估血管紧张素转换酶（ACE）活性，并通过 Western blot 评估 AT1 和 Mas 受体的蛋白表达。
与 AS-Sed 组相比，AS-Ex 组左心室壁相对厚度降低，射血分数提高；心肌细胞周期调节基因、ACE、Ang I、Ang II 和 Ang II/Ang-（1-7）比值的基因表达也降低。然而，ET 并没有诱导 Ang-（1-7）和心脏 Mas 受体表达以及心肌细胞增殖的改变。
有氧运动训练可改善收缩功能，而与心肌细胞增殖和 Ang-（1-7）/Mas 受体水平无关。然而，ET 可负性调节血管收缩/肥大轴（ACE/Ang II）并降低主动脉瓣上型主动脉狭窄大鼠心肌细胞中细胞周期负调控基因的表达。
