The classical renin-angiotensin system promotes skeletal muscle insulin resistance, atrophy, and fibrosis, whereas the nonclassical axis acts as a beneficial counter-regulator.
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.
Cabello‐Verrugio et al. (Wed,) conducted a review in Skeletal muscle pathologies (insulin resistance, atrophy, fibrosis). Classical RAS inhibition and nonclassical RAS stimulation was evaluated. The classical renin-angiotensin system promotes skeletal muscle insulin resistance, atrophy, and fibrosis, whereas the nonclassical axis acts as a beneficial counter-regulator.