title: 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, 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.
authors.affiliation: 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.
authors.forename: Tiago
authors.initials: T
authors.lastname: Fernandes
authors.forename: Nara Y
authors.initials: NY
authors.lastname: Hashimoto
authors.forename: Flávio C
authors.initials: FC
authors.lastname: Magalhães
authors.forename: Fernanda B
authors.initials: FB
authors.lastname: Fernandes
authors.forename: Dulce E
authors.initials: DE
authors.lastname: Casarini
authors.forename: Adriana K
authors.initials: AK
authors.lastname: Carmona
authors.forename: José E
authors.initials: JE
authors.lastname: Krieger
authors.forename: M Ian
authors.initials: MI
authors.lastname: Phillips
authors.forename: Edilamar M
authors.initials: EM
authors.lastname: Oliveira
mesh_terms: D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D005260:Female; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D035683:MicroRNAs; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)