Skeletal Muscle MicroRNA Patterns in Response to a Single Bout of Exercise in Females: Biomarkers for Subsequent Training Adaptation?

microRNAs (miRs) have been proposed as a promising new class of biomarkers in the context of training adaptation. Using microarray analysis, we studied skeletal muscle miR patterns in sedentary young healthy females (n = 6) before and after a single submaximal bout of endurance exercise ('reference training'). Subsequently, participants were subjected to a structured training program, consisting of six weeks of moderate-intensity continuous endurance training (MICT) and six weeks of high-intensity interval training (HIIT) in randomized order. In vastus lateralis muscle, we found significant downregulation of myomiRs, specifically miR-1, 133a-3p, and -5p, -133b, and -499a-5p. Similarly, exercise-associated miRs-23a-3p, -378a-5p, -128-3p, -21-5p, -107, -27a-3p, -126-3p, and -152-3p were significantly downregulated, whereas miR-23a-5p was upregulated. Furthermore, in an untargeted approach for differential expression in response to acute exercise, we identified n = 35 miRs that were downregulated and n = 20 miRs that were upregulated by factor 4.5 or more. Remarkably, KEGG pathway analysis indicated central involvement of this set of miRs in fatty acid metabolism. To reproduce these data in a larger cohort of all-female subjects (n = 29), qPCR analysis was carried out on n = 15 miRs selected from the microarray, which confirmed their differential expression. Furthermore, the acute response, i.e., the difference between miR concentrations before and after the reference training, was correlated with changes in maximum oxygen uptake (V̇O2max) in response to the training program. Here, we found that miRs-199a-3p and -19b-3p might be suitable acute-response candidates that correlate with individual degrees of training adaptation in females.

miRNAs as markers for the development of individualized training regimens: A pilot study.

Small, non-coding RNAs (microRNAs) have been shown to regulate gene expression in response to exercise in various tissues and organs, thus possibly coordinating their adaptive response. Thus, it is likely that differential microRNA expression might be one of the factors that are responsible for different training responses of different individuals. Consequently, determining microRNA patterns might be a promising approach toward the development of individualized training strategies. However, little is known on (1) microRNA patterns and their regulation by different exercise regimens and (2) possible correlations between these patterns and individual training adaptation. Here, we present microarray data on skeletal muscle microRNA patterns in six young, female subjects before and after six weeks of either moderate-intensity continuous or high-intensity interval training on a bicycle ergometer. Our data show that n = 36 different microRNA species were regulated more than twofold in this cohort (n = 28 upregulated and n = 8 downregulated). In addition, we correlated baseline microRNA patterns with individual changes in VO2 max and identified some specific microRNAs that might be promising candidates for further testing and evaluation in the future, which might eventually lead to the establishment of microRNA marker panels that will allow individual recommendations for specific exercise regimens.

Responders and non-responders to aerobic exercise training: beyond the evaluation of V˙O2max.

The evaluation of the maximal oxygen uptake ( V˙O2max ) following exercise training is the classical assessment of training effectiveness. Research has lacked in investigating whether individuals that do not respond to the training intervention ( V˙O2max ), also do not improve in other health-related parameters. We aimed to investigate the cardiovascular and metabolic adaptations (i.e., performance, body composition, blood pressure, vascular function, fasting blood markers, and resting cardiac function and morphology) to exercise training among participants who showed different levels of V˙O2max responsiveness. Healthy sedentary participants engaged in a 6-week exercise training program, three times a week. Our results showed that responders had a greater increase in peak power output, second lactate threshold, and microvascular responsiveness, whereas non-responders had a greater increase in cycling efficiency. No statistical differences were observed in body composition, blood pressure, fasting blood parameters, and resting cardiac adaptations. In conclusion, our study showed, for the first time, that in addition to the differences in the V˙O2max , a greater increase in microvascular responsiveness in responders compared to non-responders was observed. Additionally, responders and non-responders did not show differences in the adaptations on metabolic parameters. There is an increasing need for personalized training prescription, depending on the target clinical outcome.

Individual cardiovascular responsiveness to work-matched exercise within the moderate- and severe-intensity domains.

PURPOSE: We investigated the cardiovascular individual response to 6 weeks (3×/week) of work-matched within the severe-intensity domain (high-intensity interval training, HIIT) or moderate-intensity domain (moderate-intensity continuous training, MICT). In addition, we analyzed the cardiovascular factors at baseline underlying the response variability. METHODS: 42 healthy sedentary participants were randomly assigned to HIIT or MICT. We applied the region of practical equivalence-method for identifying the levels of responders to the maximal oxygen uptake (V̇O2max) response. For investigating the influence of cardiovascular markers, we trained a Bayesian machine learning model on cardiovascular markers. RESULTS: Despite that HIIT and MICT induced significant increases in V̇O2max, HIIT had greater improvements than MICT (p < 0.001). Greater variability was observed in MICT, with approximately 50% classified as "non-responder" and "undecided". 20 "responders", one "undecided" and no "non-responders" were observed in HIIT. The variability in the ∆V̇O2max was associated with initial cardiorespiratory fitness, arterial stiffness, and left-ventricular (LV) mass and LV end-diastolic diameter in HIIT; whereas, microvascular responsiveness and right-ventricular (RV) excursion velocity showed a significant association in MICT. CONCLUSION: Our findings highlight the critical influence of exercise-intensity domains and biological variability on the individual V̇O2max response. The incidence of "non-responders" in MICT was one third of the group; whereas, no "non-responders" were observed in HIIT. The incidence of "responders" was 11 out of 21 participants in MICT, and 20 out of 21 participants in HIIT. The response in HIIT showed associations with baseline fitness, arterial stiffness, and LV-morphology; whereas, it was associated with RV systolic function in MICT.

Comparison of morphological and functional adaptations of the heart in highly trained triathletes and long-distance runners using cardiac magnetic resonance imaging.

"Athlete's heart" is characterized by an increase in ventricular chamber sizes and myocardial mass (MM), and is mainly observed in endurance athletes. At present, it remains unclear whether cardiac adaptations in long-distance runners differ from those in triathletes. Twenty male triathletes (mean age 38.7 ± 6.2 years) and 20 male marathon runners (mean age 44.1 ± 7.9) underwent cardiac magnetic resonance imaging to calculate left and right ventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and MM. Late-enhancement (LE) imaging was used to exclude structural alterations or myocardial scarring. EDV, ESV, SV, and EF for the left and right ventricles, as well as MM, did not differ between long-distance runners and triathletes, although the weekly training volume was significantly higher in triathletes (17.05 vs 9.95 h/week, P < 0.0001). There was a significant correlation between weekly training volume and right and left EDV, right and left ESV as well as MM within the study group. Myocardial LE was absent in all athletes. Highly trained male long-distance runners and triathletes have comparable cardiac parameters. However, the extent of physical training seems to be associated with the degree of cardiac adaptation in endurance athletes. The absence of LE supports the idea that athlete's heart is a nonpathological adaptation of the cardiovascular system.

Correlation between ECG abnormalities and cardiac parameters in highly trained asymptomatic male endurance athletes: evaluation using cardiac magnetic resonance imaging.

Intensive endurance training can induce abnormal ECG patterns at rest. These alterations are differentiated into minor, mildly or distinctly abnormal ECG patterns. Echocardiographic data imply a correlation between the extent of these alterations and cardiac parameters like cardiac volume or wall thickness. In comparison to echocardiography, cardiac magnetic resonance imaging (MRI) is characterized by high reproducibility and accuracy. The aim of this study was to investigate the correlation between ECG alterations and cardiac parameters in highly trained asymptomatic male endurance athletes as assessed using cardiac MRI. Forty-five asymptomatic male endurance athletes (mean age 40 ± 8.9 years., range 19-59 years., 13 ± 5 h of training per week) underwent a cardiac MRI examination in addition to a resting ECG. Based on the ECG patterns at rest, the athletes were divided into groups with normal or minor (group 1) and mild or distinct (group 2) alterations. Steady-state free-precession cine MRI was used to calculate left and right ventricular end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, and myocardial mass (MM). Late enhancement imaging was used to exclude structural alterations or myocardial scarring. Athletes in group 1 and 2 did not differ significantly in terms of age, height, body weight, body mass index or hours of training per week. Athletes with mildly or distinctly abnormal ECG patterns showed a significantly higher MM than athletes with minor ECG alterations at rest or normal resting ECG values (156.4 ± 18.4 g vs. 140.5 ± 20.0 g; p = 0.0103). The differences persisted when the values were corrected for body surface area (80.0 ± 7.4 g/m² vs. 73.4 ± 8.3 g; p = 0.0093). All other assessed cardiac parameters did not differ between the two groups. Pathological myocardial enhancement was detected only in one patient with a minor abnormal ECG. Male asymptomatic endurance athletes with mildly or distinctly abnormal ECG patterns at rest are characterized by a higher myocardial mass than comparable athletes with minor alterations or normal ECG at rest. Thus, the extent of ECG-abnormalities seems to be mainly the result of an increase in myocardial mass. Additionally, the absence of mild or distinct ECG alterations does not exclude the presence of pathological late gadolinium enhancement.