mTOR signaling-related microRNAs as cardiac hypertrophy modulators in high-volume endurance training.

Aerobic exercise training (ET) promotes cardiovascular adaptations, including physiological left ventricular hypertrophy (LVH). However, the molecular mechanisms underlying these changes are unclear. The study aimed to elucidate specific microRNAs (miRNAs) and target genes involved with the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling in high-volume ET-induced LVH. Eight-week-old female Wistar rats were assigned to three groups: sedentary control (SC), trained protocol 1 (P1), and trained protocol 2 (P2). P1 consisted of 60 min/day of swimming, 5 times/wk, for 10 wk. P2 consisted of the same protocol as P1 until the 8th week; in the 9th week rats trained 2 times/day, and in the 10th week they trained 3 times/day. Subsequently, structure and molecular parameters were evaluated in the heart. Trained groups demonstrate higher values of peak oxygen uptake ([Formula: see text]), exercise tolerance, and LVH in a volume-dependent manner. The miRNA-26a-5p levels were higher in P1 and P2 compared with the SC group (150 ± 15%, d = 1.8; 148 ± 16%, d = 1.7; and 100 ± 7%, respectively; P < 0.05). In contrast, miRNA-16-5p levels were lower in P1 and P2 compared with the SC group (69 ± 5%, d = 2.3, P < 0.01; 37 ± 4%, d = 5.6, P < 0.001; and 100 ± 6%, respectively). Additionally, miRNA-16-5p knockdown and miRNA-26a-5p overexpression significantly promoted cardiomyocyte hypertrophy in neonatal rat cardiomyocytes. Both miRNAs were selected, with the DIANA Tools bioinformatics website, for acting in the mTOR signaling pathway. The protein expression of AKT, MTOR, ribosomal protein S6 kinase beta-1 (P70S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) were greater in P1 and even more pronounced in P2. Nonetheless, glycogen synthase kinase 3 beta (GSK3ß) protein expression was lower in trained groups. Together, these molecular changes may contribute to a pronounced physiological LVH observed in high-volume aerobic training.NEW & NOTEWORTHY Physiological hypertrophic growth of the heart as a compensatory response to exercise training (ET) is coupled with recent progress in dissecting the microRNA (miRNA)-mediated molecular basis of hypertrophy. Aerobic ET seems to reduce miRNA-16-5p and increase miRNA-26a-5p expression in a volume-dependent mode, activating protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathways, and likely produces an enhanced left ventricular hypertrophy (LVH) in high-volume endurance training. New insight into these mechanisms can be useful in understanding physiological LVH and how it might be harnessed as a therapeutic application.

Corrigendum to "Exercise Training Restores Cardiac MicroRNA-1 and MicroRNA-29c to Nonpathological Levels in Obese Rats".

[This corrects the article DOI: 10.1155/2017/1549014.].

Exercise Training Restores Cardiac MicroRNA-1 and MicroRNA-29c to Nonpathological Levels in Obese Rats.

We previously reported that aerobic exercise training (AET) consisted of 10 weeks of 60-min swimming sessions, and 5 days/week AET counteracts CH in obesity. Here, we evaluated the role of microRNAs and their target genes that are involved in heart collagen deposition and calcium signaling, as well as the cardiac remodeling induced by AET in obese Zucker rats. Among the four experimental Zucker groups: control lean rats (LZR), control obese rats (OZR), trained lean rats (LZR + TR), and trained obese rats (OZR + TR), heart weight was greater in the OZR than in the LZR group due to increased cardiac intramuscular fat and collagen. AET seems to exert a protective role in normalizing the heart weight in the OZR + TR group. Cardiac microRNA-29c expression was decreased in OZR compared with the LZR group, paralleled by an increase in the collagen volumetric fraction (CVF). MicroRNA-1 expression was upregulated while the expression of its target gene NCX1 was decreased in OZR compared with the LZR group. Interestingly, AET restored cardiac microRNA-1 to nonpathological levels in the OZR-TR group. Our findings suggest that AET could be used as a nonpharmacological therapy for the reversal of pathological cardiac remodeling and cardiac dysfunction in obesity.

Swimming training in rats increases cardiac MicroRNA-126 expression and angiogenesis.

PURPOSE: MicroRNA (miRNA)-126 is angiogenic and has two validated targets: Sprouty-related protein 1 (Spred-1) and phosphoinositol-3 kinase regulatory subunit 2 (PI3KR2), negative regulators of angiogenesis by VEGF pathway inhibition. We investigated the role of swimming training on cardiac miRNA-126 expression related to angiogenesis. METHODS: Female Wistar rats were assigned to three groups: sedentary (S), training 1 (T1, moderate volume), and training 2 (T2, high volume). T1 consisted of 60 min·d of swimming, five times per week for 10 wk with 5% body overload. T2 consisted of the same protocol of T1 until the eighth week; in the ninth week, rats trained for two times a day, and in the 10th week, rats trained for three times a day. MiRNA and PI3KR2 gene expression analysis was performed by real-time polymerase chain reaction in heart muscle. We assessed markers of training, the cardiac capillary-fiber ratio, cardiac protein expression of VEGF, Spred-1, Raf-1/ERK 1/2, and PI3K/Akt/eNOS. RESULTS: The cardiac capillary-fiber ratio increased in T1 (58%) and T2 (101%) compared with S. VEGF protein expression was increased 42% in T1 and 108% in T2. Cardiac miRNA-126 expression increased 26% (T1) and 42% (T2) compared with S, correlated with angiogenesis. The miRNA-126 target Spred-1 protein level decreased 41% (T1) and 39% (T2), which consequently favored an increase in angiogenic signaling pathway Raf-1/ERK 1/2. On the other hand, the gene expression of PI3KR2, the other miRNA-126 target, was reduced 39% (T1) and 78% (T2), and there was an increase in protein expression of components of the PI3K/Akt/eNOS signaling pathway in the trained groups. CONCLUSIONS: This study showed that aerobic training promotes an increase in the expression of miRNA-126 and that this may be related to exercise-induced cardiac angiogenesis, by indirect regulation of the VEGF pathway and direct regulation of its targets that converged in an increase in angiogenic pathways, such as MAPK and PI3K/Akt/eNOS.