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      Regulation of cardiac microRNAs induced by aerobic exercise training during heart failure.

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          Abstract

          Exercise training (ET) has beneficial effects on the myocardium in heart failure (HF) patients and in animal models of induced cardiac hypertrophy and failure. We hypothesized that if microRNAs (miRNAs) respond to changes following cardiac stress, then myocardial profiling of these miRNAs may reveal cardio-protective mechanisms of aerobic ET in HF. We used ascending aortic stenosis (AS) inducing HF in Wistar rats. Controls were sham-operated animals. At 18 wk after surgery, rats with cardiac dysfunction were randomized to 10 wk of aerobic ET (HF-ET) or to a heart failure sedentary group (HF-S). ET attenuated cardiac remodeling as well as clinical and pathological signs of HF with maintenance of systolic and diastolic function when compared with that of the HF-S. Global miRNA expression profiling of the cardiac tissue revealed 53 miRNAs exclusively dysregulated in animals in the HF-ET, but only 11 miRNAs were exclusively dysregulated in the HF-S. Out of 23 miRNAs that were differentially regulated in both groups, 17 miRNAs exhibited particularly high increases in expression, including miR-598, miR-429, miR-224, miR-425, and miR-221. From the initial set of deregulated miRNAs, 14 miRNAs with validated targets expressed in cardiac tissue that respond robustly to ET in HF were used to construct miRNA-mRNA regulatory networks that revealed a set of 203 miRNA-target genes involved in programmed cell death, TGF-β signaling, cellular metabolic processes, cytokine signaling, and cell morphogenesis. Our findings reveal that ET attenuates cardiac abnormalities during HF by regulating cardiac miRNAs with a potential role in cardio-protective mechanisms through multiple effects on gene expression.

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          Author and article information

          Journal
          Am. J. Physiol. Heart Circ. Physiol.
          American journal of physiology. Heart and circulatory physiology
          American Physiological Society
          1522-1539
          0363-6135
          Nov 15 2015
          : 309
          : 10
          Affiliations
          [1 ] From the Department of Morphology, São Paulo State University, Botucatu, São Paulo, Brazil; and.
          [2 ] Department of Internal Medicine, São Paulo State University, Botucatu, São Paulo, Brazil.
          [3 ] From the Department of Morphology, São Paulo State University, Botucatu, São Paulo, Brazil; and rcarvalho@ibb.unesp.br.
          Article
          ajpheart.00941.2014
          10.1152/ajpheart.00941.2014
          26408546
          7dd2a714-666b-4af5-952e-df5916bb19e9
          History

          aortic stenosis,cardiac stress,exercise training,heart failure,stress-regulated miRNAs

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