AUTHOR=Witvrouwen Isabel , Gevaert Andreas B. , Possemiers Nadine , Ectors Bert , Stoop Tibor , Goovaerts Inge , Boeren Evi , Hens Wendy , Beckers Paul J. , Vorlat Anne , Heidbuchel Hein , Van Craenenbroeck Amaryllis H. , Van Craenenbroeck Emeline M. 

TITLE=Plasma-Derived microRNAs Are Influenced by Acute and Chronic Exercise in Patients With Heart Failure With Reduced Ejection Fraction

JOURNAL=Frontiers in Physiology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.736494

DOI=10.3389/fphys.2021.736494

ISSN=1664-042X

ABSTRACT=Background. 
Exercise training improves VO2peak in heart failure with reduced ejection fraction (HFrEF), but the effect is highly variable as it is dependent on peripheral adaptations. We evaluated changes in plasma-derived miRNAs by acute and chronic exercise to investigate whether these can mechanistically be involved in the variability of exercise-induced adaptations. 

Methods. 
Twenty-five male HFrEF patients (left ventricular ejection fraction <40%, New York Heart Association class ≥II) participated in a 15-week combined strength and aerobic training programme. The effect of training on plasma miRNA levels was compared to 21 male age-matched sedentary HFrEF controls. Additionally, the effect of a single acute exercise bout on plasma miRNA levels was assessed. Levels of 5 miRNAs involved in pathways relevant for exercise adaptation (miR-23a, miR-140, miR-146a, miR-191 and miR-210) were quantified using RT-qPCR and correlated with cardiopulmonary exercise test, echocardiographic, vascular function and muscle strength variables. 

Results.
Expression levels of miR-146a decreased with training compared to controls. Acute exercise resulted in a decrease in miR-191 before, but not after training. Baseline miR-23a predicted change in VO2peak independent of age and left ventricular ejection fraction. Baseline miR-140 was independently correlated with change in load at the respiratory compensation point and change in body mass index, and baseline miR-146a with change in left ventricular mass index.

Conclusions. 
Plasma-derived miRNAs may reflect the underlying mechanisms of exercise-induced adaptation. In HFrEF patients, baseline miR-23a predicted VO2peak response to training. Several miRNAs were influenced by acute or repeated exercise. These findings warrant exploration in larger patient populations and further mechanistic in-vitro studies on their molecular involvement.