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)

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. (Hypertension. 2011;58:182-189.).Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Technologico-Pos-DoutoradoConselho Nacional de Desenvolvimento Cientifico e Technologico, BrazilCoordenacao de Aperfeicoamento de Pessoal de NivelNational Institutes of HealthUniv São Paulo, Sch Phys Educ & Sport, Lab Biochem & Mol Biol Exercise, BR-05508900 São Paulo, BrazilUniv São Paulo, Sch Med, InCor, Lab Genet & Mol Cardiol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Kidney & Hypertens Hosp, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilKeck Grad Inst, Lab Stem Cells, Claremont, CA USAUniversidade Federal de São Paulo, Div Nephrol, Kidney & Hypertens Hosp, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilFAPESP: 2009/18370-3FAPESP: 07/56771-4Conselho Nacional de Desenvolvimento Cientifico e Technologico-Pos-Doutorado: 200994/2007-7National Institutes of Health: 1 R01 HL 077602Web of Scienc