Aerobic Exercise Training–Induced Left Ventricular Hypertrophy Involves Regulatory MicroRNAs, Decreased Angiotensin-Converting Enzyme-Angiotensin II, and Synergistic Regulation of Angiotensin-Converting Enzyme 2-Angiotensin (1-7)

Abstract

Aerobic exercise training leads to a physiological, non pathological left ventricular hypertrophy (LVH); however, the underlying biochemical and molecular mechanisms of physiological LVH are unknown. The role of microRNAs regulating the classic and the novel cardiac renin angiotensin system (RAS) was studied in trained rats assigned to three groups: sedentary, swimming trained with protocol 1 (T1: moderate volume training) and protocol 2 (T2: high volume training). Cardiac Ang I levels, ACE activity and protein expression, as well as Ang II levels were lower in T1 and T2, however AT1 mRNA levels (69% in T1 and 99% in T2) and protein expression (240% in T1 and 300% in T2) increased after training. AT2 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. LVH induced by aerobic training involves microRNAs regulation and an increase in cardiac AT1 receptor without the participation of Ang II. Parallel to this, increase in ACE2, Ang (1–7) and AT2 receptor in the heart by exercise suggests that this non classic cardiac RAS counteracts the classic cardiac RAS. These findings are consistent with a model in which exercise may induce LVH, at least in part, altering the expression of specific microRNAs targeting RAS genes. Together these effects might provide the additional aerobic capacity required by the exercised heart.

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

“…Interestingly, in a recent study (41) we showed that cardiac AGT and Ang I levels, ACE activity and protein expression, as well as Ang II levels were lower in swimming-trained rats, although AT1 receptor levels increased after training. In addition, ACE2 and Ang (1-7) levels were increased in the hearts of swimming-trained rats.…”

“…Interestingly, we recently showed that AT1 receptor blockade prevents physiological left ventricle hypertrophy induced by resistance training (17) and aerobic exercise training (19,41). These studies underscore the importance of a better understanding of aerobic and resistance training and the regulation of left ventricle hypertrophy by the RAS (Figure 2).…”

“…The exercise training decreased miR-143 that could up-regulate cardioprotective genes such as ACE2, and also increased miRNA-27 that could down-regulate cardiac ACE expression. Together these effects might provide the additional aerobic capacity required by the exercised heart (41).…”

O grau de melhora na função das células progenitoras endoteliais derivadas da medula óssea é dependente do volume de treinamento físico aeróbio

“…Among the autonomic and hemodynamic adaptations which will influence the cardiovascular system, resting bradycardia consists in a good functional parameter to verify the adaptation and efficiency of the aerobic ET; therefore, it is considered an ET physiological marker. This adaptation is observed both in experimentation animals 20,21,23 and humans 24 .…”

“…This training protocol with increase of exercise volume has been used with the purpose to mimic a high-performance exercise training 21 . The used protocols were characterized as low and moderate intensity and long duration trainings, being efficient in promoting cardiovascular adaptations and increase of muscular oxidative capacity 20,21 . Pre and post the ET period, the animals were submitted to hemodynamic analyses, exercise tolerance test and oxygen uptake peak.…”