MicroRNAs 29 are involved in the improvement of ventricular compliance promoted by aerobic exercise training in rats

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 ϭ 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 2ϫ/day, and on the 10th wk 3ϫ/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 ␣-actin, ␣/␤-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 ϭ 0.61, P Ͻ 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. cardiac hypertrophy; collagen; molecular markers; swimming training; physiological cardiac hypertrophy; diastolic function microRNAs (miRNAs) are recognized as a new class of gene expression regulators, consisting of short RNAs, singlestranded, that do not synthesize proteins.MiRNAs are currently potential therapeutic targets and biomarkers in cardiovascular research of various physiological and pathological processes (2,3,(33)(34)(35)(36)(37)40). The action of miRNAs occurs at the posttranscriptional level. MiRNAs negatively regulate the expression of their target genes by coupling to the 3=-untranslated regions (3=-UTR) of mRNA expressed by the target gene (direct modulation) or in the 3=-UTR of mRNA related with the expression of target gene (indirect modulation), which represses its translation into protein (18,19).There are several studies involving miRNAs in pathological cardiac hypertrophy (CH) (2, 3, 29, 35, 36). MiRNAs-1, 133a, and 133b are the best known and highly expressed in heart (36) and already have several targets genes validated, as transcription factors, proteins involved in cellular growth and division, rearrangement of myofibrils and cardiac contractility (34). Carè et al. (2) reported that the decreased expression of miRNA-1 and 133 in vivo and in vitro has a critical role in hypertro...

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

“…In contrast, pathological cardiac hypertrophy did not activate the Akt signal cascade and in some cases the absence of Akt1 profoundly exacerbated the transverse aortic constriction or endothelin 1-stimulated pathological cardiac hypertrophic, suggesting that the Akt activation pathway may differentiate between physiological and pathological hypertrophy (44,45). Accordingly, we observed that the swimming training protocols increased the cardiac phosphoSer 473 -Akt protein expression, indicating its participation in physiological cardiac hypertrophy (20). Therefore, in a recent study we showed that a session of strength exercise consisting of 4 sets of 12 repetitions with an 80% work overload promoted increased Akt activity in a group exercised and killed 30 min after the strength training session.…”

“…Our results showed that the first swimming training protocol did not modify the gene expression of ANF, skeletal α-actin or α/β-MHC, whereas the second training protocol significantly reduced the left ventricle levels of skeletal α-actin by 53% and increased the left ventricle levels of α/β-MHC by 98% (20). α-MHC has been associated with increased myosin ATPase activity and enhancement of contractility, corroborating the improvement of ventricular function observed with aerobic training (21).…”

“…We showed that the expression of miR-1, 133a and 133b was similar to the expression in pathological and concentric cardiac hypertrophy. Additionally, miR-1, 133a and 133b are similarly down-regulated in both aerobically trained groups related www.bjournal.com.br Braz J Med Biol Res 44 (9) 2011 to sedentary animals, also showing a common pattern of expression that suggests an involvement in general programs for cardiac hypertrophy (Figure 3) (20). However, there is an unanswered question about whether other miRs are differentially expressed in physiological cardiac hypertrophy when compared to the pathological type and thus further investigation is necessary to delineate and differentiate the expression of miRs in concentric and eccentric cardiac physiological hypertrophy (Figure 4).…”

“…Although cardiac hypertrophy induced by treadmill and swimming training is commonly observed, in some cases these types of training have failed to induce cardiac hypertrophy (24). We have observed that swimming training induces robust cardiac hypertrophy when compared to treadmill training in rats and mice (19,20,22,24,25). In fact, a different cardiac adaptation should be expected after swimming training, since this training www.bjournal.com.br Braz J Med Biol Res 44 (9) 2011 mode differs from running training with respect to body position in the water, water pressure and temperature regulation.…”

“…MiRs are short, single-stranded RNAs that have few nucleotides (17)(18)(19)(20)(21)(22), and work as "brakes" for many cellular processes, since they regulate the protein expression of target genes. The mechanism of action of an miR is called post-transcriptional, i.e., these molecules are coupled with partial complementarity in regions 3' untranslated mRNA targets, inhibiting the translation of the mRNA into a protein.…”