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Background Exercise training (ET) improves aerobic capacity (VO2peak) in heart failure with reduced ejection fraction (HFrEF), but the individual response is highly variable. Underlying mechanisms of this variability are still not fully elucidated yet. Specific miRNA might be involved in cardiovascular adaptation to exercise, as changes in miRNA levels with repetitive acute exercise bouts have been described. miR-23a, -140, -146a, -191 and -210 have been related to aerobic capacity, endothelial function and angiogenesis. Purpose First, to evaluate if vascular function-associated miRNAs are related to vascular function and aerobic capacity in HFrEF patients. Second, to evaluate the effect of a single exercise bout on the miR profile. Third, to evaluate if miRNA changes in response to acute exercise are related to aerobic and vascular response to training. Methods Plasma levels of miR-23a, -140, -146a, -191 and -210 were analyzed using RT-qPCR in 24 HFrEF patients, before and immediately after a cardiopulmonary exercise test (CPET) and repeated after 15 weeks of ET. At baseline and after 15 weeks, VO2peak, flow-mediated dilation (FMD), pulsed wave velocity (PWV) and heart rate-corrected augmentation index (Aix@75) were recorded. Results In this prospective study, 24 HFrEF patients were included. Mean age was 56.9±12.9 years, mean left ventricular ejection fraction 31.7±7.0% and median adherence to ET was 41 sessions (30–43). Mean percent change in VO2peak was 2.86% (±13.5), in Aix@75 −9.8% (±80.9), in FMD 79.1% (±223.7) and in PWV −3.1% (±11.2), however these changes were not significant compared to baseline (p&amp;gt;0.05). At baseline, none of the miRNA were correlated with percent change in VO2peak (all p&amp;gt;0.05), however, miR-140 showed a trend towards correlation (r=−0.385, p=0.063). miR-191was significantly correlated with Aix@75 at baseline and after 15 weeks (respectively r=0.588, p=0.013 and r=0.609, p=0.006) and miR-23a was significantly correlated with FMD at baseline and showed a trend at 15 weeks (respectively r=0.462, p=0.040 and r=0.417, p=0.076). An acute exercise bout resulted in a significant decrease of miR-191 (1.82 before and 1.58 after CPET; 14% decrease, p=0.043). This change was significantly correlated with percent change in Aix@75 (r=−0.730, p=0.005) after ET. In a linear regression model adjusted for age, change in miR-191 significantly predicted percent change in Aix@75 (B=−84.5, p=0.043). Conclusion In HFrEF patients, plasma levels of miR-191 significantly decrease in response to an acute exercise bout. Baseline levels of vascular function-associated miRNAs were correlated with arterial stiffness and endothelial function before and after exercise training, which may suggest that these miRNAs are implicated in the vascular adaptations due to repetitive acute exercise bouts. However, these findings need to be validated in larger cohorts. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fund for scientific research-Flanders (FWO)

The effect of an acute exercise bout on plasme miRNA and its relation with cardiovascular adaptation to exercise training in heart failure