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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)
Authors: Fernandes, Tiago
Hashimoto, Nara Y.
Magalhaes, Flavio C.
Fernandes, Fernanda Barrinha [UNIFESP]
Casarini, Dulce Elena [UNIFESP]
Carmona, Adriana Karaoglanovic [UNIFESP]
Krieger, Jose E.
Phillips, M. Ian
Oliveira, Edilamar M.
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Keck Grad Inst
Keywords: aerobic exercise training
cardiac hypertrophy
renin angiotensin system
angiotensin II receptors
angiotensin (1-7)
Issue Date: 1-Aug-2011
Publisher: Lippincott Williams & Wilkins
Citation: Hypertension. Philadelphia: Lippincott Williams & Wilkins, v. 58, n. 2, p. 182-U121, 2011.
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. (Hypertension. 2011;58:182-189.).
ISSN: 0194-911X
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