Possible role for microRNAs to identify patients at risk for an exercise-induced cardiac event

Abstract

Background and objective Acute exercise is a trigger of cardiac events even in patients with unknown or stable cardiac disease and there’s a paucity of biomarkers that could possibly identify patients at risk. Several micro ribonucleic acids (miRNAs), which are small non-coding RNA molecules that control gene expression by translational inhibition, however, have been associated with atherogenesis and coronary artery disease (CAD). We set out to assess in a great number of atherogenic miRNAs whether their responsiveness to an acute bout of exercise differed between healthy subjects and patients with CAD. Methods In this study, 40 participants (10 healthy males and 10 healthy females; 10 male and 10 female patients with CAD) performed an all-out cycle ergometry. All plasma samples were extracted for total RNA before and after exercise. Each sample was analyzed via quantitative reverse transcription polymerase chain reaction (qRT-PCR) for a set of 187 potential target miRNAs, initially validated by a screening array and by literature. In this analysis we focused on miRNAs known to be associated with atherogenesis. Results 77 miRNAs were responsive to a single all-out exercise in one or both groups (all p<.05). Focusing on atherogenic miRNAs, five were significantly modulated in both groups. The antiatherogenic miR-143-3p; miR-145-5p and miR-23b-3p showed stronger up-regulation and the proatherogenic miR-17-5p and miR-92a-3p a weaker down regulation in healthy subjects compared to CAD patients. Additional five miRNAs were significantly modulated only in the CAD patients and two miRNA only in the healthy participants. Using a multi variance analysis, significant differences between groups could be confirmed for the anti-atherogenic miR-101-3p, which showed a significant down regulation in the CAD patients, but a slightly up regulation in the healthy participants. Conclusion This study shows that miRNAs respond differently to an acute bout of exercise in healthy subjects as compared to CAD patients. By further characterizing a panel of responsive and atherogenic miRNAs it may eventually be possible to evaluate the atheroprotective state of CAD patients and to identify patients at risk for an exercise-induced cardiac event

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