INCT NanoBioFar, Department of Physiology and Biophysics, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
Peptides. 2012 Nov;38(1):54-61. doi: 10.1016/j.peptides.2012.05.024. Epub 2012 Aug 18.
The renin-angiotensin system (RAS) is involved in the cardiac and vascular remodeling associated with cardiovascular diseases. Angiotensin (Ang) II/AT(1) axis is known to promote cardiac hypertrophy and collagen deposition. In contrast, Ang-(1-7)/Mas axis opposes Ang II effects in the heart producing anti-trophic and anti-fibrotic effects. Exercise training is known to induce cardiac remodeling with physiological hypertrophy without fibrosis. We hypothesize that cardiac remodeling induced by chronic exercise depends on the action of Ang-(1-7)/Mas axis. Thus, we evaluated the effect of exercise training on collagen deposition and RAS components in the heart of FVB/N mice lacking Mas receptor (Mas-KO). Male wild-type and Mas-KO mice were subjected to a moderate-intense swimming exercise training for 6 weeks. The left ventricle (LV) of the animals was sectioned and submitted to qRT-PCR and histological analysis. Circulating and tissue angiotensin peptides were measured by RIA. Sedentary Mas-KO presented a higher circulating Ang II/Ang-(1-7) ratio and an increased ACE2 expression in the LV. Physical training induced in Mas-KO and WT a similar cardiac hypertrophy accompanied by a pronounced increase in collagen I and III mRNA expression. Trained Mas-KO and trained WT presented increased Ang-(1-7) in the blood. However, only in trained-WT there was an increase in Ang-(1-7) in the LV. In summary, we showed that deletion of Mas in FVB/N mice produced an unbalance in RAS equilibrium increasing Ang II/AT(1) arm and inducing deleterious cardiac effects as deposition of extracellular matrix proteins. These data indicate that Ang-(1-7)/Mas axis is an important counter-regulatory mechanism in physical training mediate cardiac adaptations.
肾素-血管紧张素系统（RAS）参与心血管疾病相关的心脏和血管重塑。血管紧张素（Ang）II/AT1 轴已知可促进心脏肥大和胶原沉积。相比之下，Ang-(1-7)/Mas 轴在心脏中产生抗营养和抗纤维化作用，拮抗 Ang II 的作用。运动训练已知可引起心脏生理性肥大而无纤维化的重塑。我们假设慢性运动引起的心脏重塑依赖于 Ang-(1-7)/Mas 轴的作用。因此，我们评估了运动训练对缺乏 Mas 受体（Mas-KO）的 FVB/N 小鼠心脏胶原沉积和 RAS 成分的影响。雄性野生型和 Mas-KO 小鼠接受中等强度的游泳运动训练 6 周。将动物的左心室（LV）切片并进行 qRT-PCR 和组织学分析。通过 RIA 测量循环和组织血管紧张素肽。久坐不动的 Mas-KO 表现出更高的循环 Ang II/Ang-(1-7) 比值和 LV 中 ACE2 表达增加。运动训练在 Mas-KO 和 WT 中引起相似的心脏肥大，伴随着胶原 I 和 III mRNA 表达的显著增加。训练有素的 Mas-KO 和训练有素的 WT 血液中的 Ang-(1-7) 增加。然而，只有在训练有素的 WT 中，LV 中的 Ang-(1-7) 才增加。总之，我们表明 FVB/N 小鼠中 Mas 的缺失导致 RAS 平衡失衡，增加 Ang II/AT1 臂，并诱导细胞外基质蛋白沉积等有害的心脏效应。这些数据表明，Ang-(1-7)/Mas 轴是运动训练中介导心脏适应的重要代偿机制。
