Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.
Med Res Rev. 2015 May;35(3):437-63. doi: 10.1002/med.21343. Epub 2015 Mar 11.
Skeletal muscle is a tissue that shows the most plasticity in the body; it can change in response to physiological and pathological stimuli. Among the diseases that affect skeletal muscle are myopathy-associated fibrosis, insulin resistance, and muscle atrophy. A common factor in these pathologies is the participation of the renin-angiotensin system (RAS). This system can be functionally separated into the classical and nonclassical RAS axis. The main components of the classical RAS pathway are angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), and Ang-II receptors (AT receptors), whereas the nonclassical axis is composed of ACE2, angiotensin 1-7 [Ang (1-7)], and the Mas receptor. Hyperactivity of the classical axis in skeletal muscle has been associated with insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports the action of the nonclassical RAS as a counter-regulator axis of the classical RAS pathway in skeletal muscle. In this review, we describe the mechanisms involved in the pathological effects of the classical RAS, advances in the use of pharmacological molecules to inhibit this axis, and the beneficial effects of stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and fibrosis in skeletal muscle.
骨骼肌是一种在体内具有最大可塑性的组织；它可以响应生理和病理刺激而发生变化。影响骨骼肌的疾病包括肌病相关纤维化、胰岛素抵抗和肌肉萎缩。这些病理学的一个共同因素是肾素-血管紧张素系统 (RAS) 的参与。该系统可以在功能上分为经典和非经典 RAS 轴。经典 RAS 途径的主要成分是血管紧张素转换酶 (ACE)、血管紧张素 II (Ang-II) 和 Ang-II 受体 (AT 受体)，而非经典轴由 ACE2、血管紧张素 1-7 [Ang (1-7)] 和 Mas 受体组成。骨骼肌中经典轴的过度活跃与胰岛素抵抗、萎缩和纤维化有关。相比之下，目前的证据支持非经典 RAS 作为骨骼肌中经典 RAS 途径的反向调节轴的作用。在这篇综述中，我们描述了经典 RAS 的病理作用所涉及的机制、使用药理学分子抑制该轴的进展，以及刺激非经典 RAS 途径对骨骼肌胰岛素抵抗、萎缩和纤维化的有益作用。
