School of Physical Education and Sport, University of Sao Paulo, Laboratory of Biochemistry and Molecular Biology of Exercise, Av Professor Mello Moraes, 65 Cidade Universitária, São Paulo 05508-900, Brazil.
Hypertension. 2011 Aug;58(2):182-9. doi: 10.1161/HYPERTENSIONAHA.110.168252. Epub 2011 Jun 27.
Aerobic exercise training leads to a physiological, nonpathological left ventricular hypertrophy; however, the underlying biochemical and molecular mechanisms of physiological left ventricular hypertrophy are unknown. The role of microRNAs regulating the classic and the novel cardiac renin-angiotensin (Ang) system was studied in trained rats assigned to 3 groups: (1) sedentary; (2) swimming trained with protocol 1 (T1, moderate-volume training); and (3) protocol 2 (T2, high-volume training). Cardiac Ang I levels, Ang-converting enzyme (ACE) activity, and protein expression, as well as Ang II levels, were lower in T1 and T2; however, Ang II type 1 receptor mRNA levels (69% in T1 and 99% in T2) and protein expression (240% in T1 and 300% in T2) increased after training. Ang II type 2 receptor mRNA levels (220%) and protein expression (332%) were shown to be increased in T2. In addition, T1 and T2 were shown to increase ACE2 activity and protein expression and Ang (1-7) levels in the heart. Exercise increased microRNA-27a and 27b, targeting ACE and decreasing microRNA-143 targeting ACE2 in the heart. Left ventricular hypertrophy induced by aerobic training involves microRNA regulation and an increase in cardiac Ang II type 1 receptor without the participation of Ang II. Parallel to this, an increase in ACE2, Ang (1-7), and Ang II type 2 receptor in the heart by exercise suggests that this nonclassic cardiac renin-angiotensin system counteracts the classic cardiac renin-angiotensin system. These findings are consistent with a model in which exercise may induce left ventricular hypertrophy, at least in part, altering the expression of specific microRNAs targeting renin-angiotensin system genes. Together these effects might provide the additional aerobic capacity required by the exercised heart.
有氧运动训练导致生理性、非病理性左心室肥厚；然而，生理性左心室肥厚的潜在生化和分子机制尚不清楚。本研究旨在探讨微 RNA 调节经典和新型心脏肾素-血管紧张素（Ang）系统的作用，将大鼠分为 3 组：（1）安静组；（2）1 方案（T1，中等容量训练）游泳训练组；（3）2 方案（T2，大运动量训练）。T1 和 T2 组大鼠心脏血管紧张素 I 水平、血管紧张素转换酶（ACE）活性和蛋白表达以及 Ang II 水平均降低；然而，Ang II 型 1 受体 mRNA 水平（T1 组降低 69%，T2 组降低 99%）和蛋白表达（T1 组增加 240%，T2 组增加 300%）增加。Ang II 型 2 受体 mRNA 水平（T2 组增加 220%）和蛋白表达（T2 组增加 332%）增加。此外，T1 和 T2 还增加了心脏 ACE2 活性和蛋白表达以及 Ang（1-7）水平。运动增加了心脏中的 microRNA-27a 和 27b，靶向 ACE，降低了 microRNA-143，靶向 ACE2。有氧运动训练引起的左心室肥厚涉及 microRNA 调节和心脏 Ang II 型 1 受体增加，而没有 Ang II 的参与。与此平行，运动使心脏中的 ACE2、Ang（1-7）和 Ang II 型 2 受体增加表明，这种非经典心脏肾素-血管紧张素系统与经典心脏肾素-血管紧张素系统相互作用。这些发现与一种模型一致，即运动至少部分通过改变针对肾素-血管紧张素系统基因的特定 microRNA 的表达，可能导致左心室肥厚。这些作用可能为运动心脏提供所需的额外有氧能力。
