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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.

Original publication

DOI

10.1152/ajpheart.00941.2014

Type

Journal article

Journal

Am J Physiol Heart Circ Physiol

Publication Date

15/11/2015

Volume

309

Pages

H1629 - H1641

Keywords

aortic stenosis, cardiac stress, exercise training, heart failure, stress-regulated miRNAs, Animals, Aortic Valve Stenosis, Apoptosis, Atrial Remodeling, Cytokines, Disease Models, Animal, Gene Expression Regulation, Heart Failure, MicroRNAs, Morphogenesis, Physical Conditioning, Animal, Rats, Rats, Wistar, Real-Time Polymerase Chain Reaction, Sedentary Behavior, Signal Transduction, Ventricular Remodeling