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.
Subject(s)
Angiotensin I/metabolism , Hypertrophy, Left Ventricular/metabolism , MicroRNAs/metabolism , Myocardium/metabolism , Peptide Fragments/metabolism , Peptidyl-Dipeptidase A/metabolism , Physical Conditioning, Animal/physiology , Angiotensin I/genetics , Angiotensin-Converting Enzyme 2 , Animals , Female , Hemodynamics , Hypertrophy, Left Ventricular/genetics , Hypertrophy, Left Ventricular/physiopathology , MicroRNAs/genetics , Peptide Fragments/genetics , Peptidyl-Dipeptidase A/genetics , Rats , Rats, Wistar , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , Renin-Angiotensin System/physiologyABSTRACT
BACKGROUND: The allele threonine (T) of the angiotensinogen has been associated with ventricular hypertrophy in hypertensive patients and soccer players. However, the long-term effect of physical exercise in healthy athletes carrying the T allele remains unknown. We investigated the influence of methionine (M) or T allele of the angiotensinogen and D or I allele of the angiotensin-converting enzyme on left-ventricular mass index (LVMI) and maximal aerobic capacity in young healthy individuals after long-term physical exercise training. DESIGN: Prospective clinical trial. METHODS: Eighty-three policemen aged between 20 and 35 years (mean+/-SD 26+/-4.5 years) were genotyped for the M235T gene angiotensinogen polymorphism (TT, n = 25; MM/MT, n = 58) and angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism (II, n = 18; DD/DI, n = 65). Left-ventricular morphology was evaluated by echocardiography and maximal aerobic capacity (VO2peak) by cardiopulmonary exercise test before and after 17 weeks of exercise training (50-80% VO2peak). RESULTS: Baseline VO2peak and LVMI were similar between TT and MM/MT groups, and II and DD/DI groups. Exercise training increased significantly and similarly VO2peak in homozygous TT and MM/MT individuals, and homozygous II and DD/DI individuals. In addition, exercise training increased significantly LVMI in TT and MM/MT individuals (76.5+/-3 vs. 86.7+/-4, P = 0.00001 and 76.2+/-2 vs. 81.4+/-2, P = 0.00001, respectively), and II and DD/DI individuals (77.7+/-4 vs. 81.5+/-4, P = 0.0001 and 76+/-2 vs. 83.5+/-2, P = 0.0001, respectively). However, LVMI in TT individuals was significantly greater than in MM/MT individuals (P = 0.04). LVMI was not different between II and DD/DI individuals. CONCLUSION: Left-ventricular hypertrophy caused by exercise training is exacerbated in homozygous TT individuals with angiotensinogen polymorphism.
