MicroRNAs 29 are involved in the improvement of ventricular compliance promoted by aerobic exercise training in rats - PubMed (original) (raw)
MicroRNAs 29 are involved in the improvement of ventricular compliance promoted by aerobic exercise training in rats
U P R Soci et al. Physiol Genomics. 2011.
Abstract
MiRNAs regulate cardiac development, hypertrophy, and angiogenesis, but their role in cardiac hypertrophy (CH) induced by aerobic training has not previously been studied. Aerobic training promotes physiological CH preserving cardiac function. This study assessed involvement of miRNAs-29 in CH of trained rats. Female Wistar rats (n=7/group) were randomized into three groups: sedentary (S), training 1 (T1), training 2 (T2). T1: swimming sessions of 60 min/5 days/wk/10 wk. T2: similar to T1 until 8th wk. On the 9th wk rats swam 2×/day, and on the 10th wk 3×/day. MiRNAs analysis was performed by miRNA microarray and confirmed by real-time PCR. We assessed: markers of training, CH by ratio of left ventricle (LV) weight/body wt and cardiomyocytes diameter, pathological markers of CH (ANF, skeletal α-actin, α/β-MHC), collagen I and III (COLIAI and COLIIIAI) by real-time PCR, protein collagen by hydroxyproline (OH-proline) concentration, CF and CH by echocardiography. Training improved aerobic capacity and induced CH. MiRNAs-1, 133a, and 133b were downregulated as observed in pathological CH, however, without pathological markers. MiRNA-29c expression increased in T1 (52%) and T2 (123%), correlated with a decrease in COLIAI and COLIIIAI expression in T1 (27%, 38%) and T2 (33%, 48%), respectively. MiRNA-29c was inversely correlated to OH-proline concentration (r=0.61, P<0.05). The E/A ratio increased in T2, indicating improved LV compliance. Thus, these results show that aerobic training increase miR-29 expression and decreased collagen gene expression and concentration in the heart, which is relevant to the improved LV compliance and beneficial cardiac effects, associated with aerobic high performance training.
Figures
Fig. 1.
Effect of different aerobic exercise training volume on cardiac hypertrophy (CH) of Wistar rats. Data are presented as means ± SD. A: CH was displayed by echocardiography (mg/g), left ventricle (LV) weight-to-body weight ratio (LV/BW, mg/g) and cardiomyocyte diameter analysis in sedentary (S, n = 7) and trained groups (T1, n = 6; T2, n = 6). Significant difference vs. *S, †T1 P < 0.05; **T1, P < 0.01. B: the increase of CH was positively correlated with the increased of VO2max (S, n = 7; T1, n = 7; T2, n = 8) (r = 0.68, P < 0.05).
Fig. 2.
Effect of swimming exercise training on classical molecular markers of cardiac hypertrophy. A: α/β-myosin heavy chain (MHC) ratio, atrial natriuretic factor (ANF), and skeletal α-actin evaluated by real-time PCR. Targeted genes were normalized by cyclophilin mRNA. B: representative blots of cardiac phosphoSer473-Akt, Akt1, and α-tubulin from S, T1, and T2 groups. C: cardiac Akt activation (represented by phosphoSer473-Akt/Akt1 ratio). Targeted bands were normalized to cardiac α-tubulin. Groups: S (n = 7), T1 (n = 6), and T2 (n = 6). Data are reported as means ± SD. Significant difference vs. *S, †T1, P < 0.05; **S, P < 0.01.
Fig. 3.
Differential expression of microRNAs (miRNAs) in LV induced by swimming exercise training. A: total of miRNAs differentially expressed by microarray: 87 miRNAs presented significant difference, 48 upregulated, 39 downregulated (P < 0.01 vs. *S). B: relative expression of miRNAs-1, 133a, 133b, 29a, 29b, and 29c related to S group by microarray (S, n = 2; T1, n = 2; T2, n = 2) (P < 0.01 vs. S). C: confirmation of differential expression of miRNAs-1, 133a, 133b, and 29c by real-time PCR reaction, percentage related to S group (%) S (n = 5), T1 (n = 5). and T2 (n = 5).
Fig. 4.
Gene and protein expression of collagen. A: collagen type I gene relative expression by real-time PCR, COLIAI (S, n = 5; T1, n = 5; T2, n = 5), collagen type III gene relative expression by real-time PCR, COLIIIAI (S, n = 5; T1, n = 5; T2, n = 5), LV collagen quantified from the hydroxyproline (OH-proline) concentration (mg/g) (S, n = 4; T1, n = 4; T2, n = 4). Values are expressed in percentage (%) from control group (Significant difference vs. *S, P < 0.05). B: the increase of miRNA-29c expression was negatively correlated with the decreased OH-proline concentration in LV (r = −0.61, P < 0.05). Significant difference vs.*S, P < 0.05.
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