Exercise-induced changes in miRNA expression in coronary artery disease.

Objectives: Micro ribonucleic acids (miRNAs) are small non-coding RNA molecules that control gene expression by translational inhibition. Exercise has been shown to affect several miRNAs' expression in healthy subjects, but this has not yet been studied in patients with coronary artery disease (CAD). Since exercise training confers beneficial long-term effects and may also trigger acute coronary events, it is of utmost interest to be able to identify those who are risk for untoward effects. Therefore, we set out to assess miRNA expression in response to maximal ergospirometry in patients with CAD.

Methods: Total RNA was extracted from blood drawn immediately before and 5 min after maximal cycle-ergospirometry (10 male and 10 female CAD patients). A qRT-PCR was performed for 187 target miRNAs associated with endothelial function/dysfunction, cardiovascular disease, myocardial infarction, and sudden cardiac death.

Results: In response to a maximal ergospirometry, 33 miRNAs significantly changed their expression levels. Of these miRNAs 16 were significantly differently expressed between gender. Using multi-variance analysis, nine miRNAs (let-7e-5p; miR-1; miR-19b-1-5p; miR-103a-3p; miR-148b-3p; miR-181b-5p; miR-188-5p; miR-423-5p; miR-874-3p) showed significantly different responses to maximal ergospirometry between genders.

Conclusions: We report for the first time that in patients with CAD, miRNA expression is amenable to maximal ergospirometry and that the extent of changes differs between genders. Affected by exercise and gender were miRNAs that are associated, among others, with pathways for glucose metabolism, oxidative stress, and angiogenesis. Future studies should assess whether disease-specific miRNA expression in response to maximal exercise might serve as a marker for patient outcome.