Circulating MicroRNA Profiling Reveals Specific Subsignatures in Response to a Maximal Incremental Exercise Test.

ABSTRACT: Fernández-Sanjurjo, M, Díaz-Martínez, ÁE, Díez-Robles, S, González-González, F, de Gonzalo-Calvo, D, Rabadán, M, Dávalos, A, Fernández-García, B, and Iglesias-Gutiérrez, E. Circulating microRNA profiling reveals specific subsignatures in response to a maximal incremental exercise test. J Strength Cond Res 35(2): 287-291, 2021-Circulating microRNAs (c-miRNAs) have been described as emergent regulators and biomarkers of exercise. The aim of this study was to analyze the c-miRNA response to a maximal incremental exercise test (MIET) and its relationship with markers of exercise response and adaptation. Two blood samples were collected from 9 male amateur runners (31-50 years), before (Pre) and after (Post) a MIET. The maximal oxygen uptake (V̇o2max), maximum heart rate (HRmax), and maximal aerobic speed (MAS) were recorded. Lactate and creatine kinase (CK) plasma concentrations were measured. A panel of 752 miRNAs was analyzed using standardized protocols and relative quantification to Pre. A total of 13 miRNAs were found significantly upregulated at Post. By focusing on the exercise markers that correlate with the expression of these miRNAs, they were clustered into different functional groups or subsignatures. Thus, miR-21-5p, miR-29b-3p, and miR-183-5p showed a strong correlation with HRmax and a validated target signature related to fatty acid metabolism. Furthermore, let-7c-5p, miR-340-5p, miR-425-3p, and miR-629-5p were significantly correlated with CK, and the most significantly enriched pathways for these subsignatures were the Hippo signaling pathway and signaling pathways regulating pluripotency of stem cells. Finally, Pre miR-106b-5p expression showed an inverse association with MAS and Post lactate concentration, which highlights its relevance as biomarker of training status and its predictive value for performance. No significant correlations were observed with V̇o2max. Our results define for the first time specific functional c-miRNA subsignatures, adding novel evidence about their potential regulatory role in exercise response.

Circulating microRNAs as emerging cardiac biomarkers responsive to acute exercise.

BACKGROUND: Circulating microRNAs (c-miRNAs) are mediators of intercellular communication with great potential as cardiac biomarkers. The analysis of c-miRNAs in response to physiological stress, such as exercise, would provide valuable information for clinical practice and a deeper understanding of the molecular response to physical activity. Here, we analysed for the first time the acute exercise response of c-miRNAs reported as biomarkers of cardiac disease in a well-characterized cohort of healthy active adults. METHODS: Blood samples were collected immediately before and after (0 h, 24 h, 72 h) a 10-km race, a half-marathon (HM) and a marathon (M). Serum RNA from 10-km and M samples was extracted and a panel of 74 miRNAs analysed using RT-qPCR. c-miRNA response was compared with a panel of nine cardiac biomarkers. Functional enrichment analysis was performed. Pre- and post-M echocardiographic analyses were carried out. RESULTS: Serum levels of all cardiac biomarkers were upregulated in a dose-dependent manner in response to exercise, even in the absence of symptoms or signs of cardiac injury. A deregulation in the profiles of 5 and 19 c-miRNAs was observed for 10-km and M, respectively. Each race induced a specific qualitative and quantitative alteration of c-miRNAs implicated in cardiac adaptions. Supporting their discriminative potential, a number of c-miRNAs previously associated with cardiac disease were undetectable or stable in response to exercise. Conversely, "pseudo-disease" signatures were also observed. CONCLUSIONS: c-miRNAs may be useful for the management of cardiac conditions in the context of acute aerobic exercise. TRANSLATIONAL ASPECTS OF THE WORK: Circulating microRNAs could offer incremental diagnostic value to established and emerging cardiac biomarkers, such as hs-cTnT or NT-proBNP, in those patients with cardiac dysfunction symptoms after an acute bout of endurance exercise. Furthermore, circulating miRNAs could also show "pseudo-disease" signatures in response to acute exercise. Clinical practitioners should be aware of the impact caused by exercise in the interpretation of miRNA data.

Circulating inflammatory miRNA signature in response to different doses of aerobic exercise.

While moderate acute exercise has been associated with strong anti-inflammatory mechanisms, strenuous exercise has been linked to deleterious inflammatory perturbations. It is therefore fundamental to elucidate the mechanisms that regulate the exercise-induced inflammatory cascade. Information on novel regulators such as circulating inflammatory microRNAs (c-inflammamiRs) is incomplete. In this study, we evaluated the response of a panel of c-inflammamiRs to different doses of acute aerobic exercise. We first studied the exercise-induced inflammatory cascade in serum samples of nine active middle-aged males immediately before and after (0 h, 24 h, 72 h) 10-km, half-marathon, and marathon races. Next, we analyzed the circulating profile of 106 specific c-inflammamiRs immediately before) and after (0 h, 24 h) 10-km (low inflammatory response) and marathon (high inflammatory response) races. Analysis of classical inflammatory parameters revealed a dose-dependent effect of aerobic exercise on systemic inflammation, with higher levels detected after marathon. We observed an increase in miR-150-5p immediately after the 10-km race. Levels of 12 c-inflammamiRs were increased immediately after the marathon (let-7d-3p, let-7f-2-3p, miR-125b-5p, miR-132-3p, miR-143-3p, miR-148a-3p, miR-223-3p, miR-223-5p, miR-29a-3p, miR-34a-5p, miR-424-3p, and miR-424-5p). c-inflammamiRs returned to basal levels after 24 h. Correlation and in silico analyses supported a close association between the observed c-inflammamiR pattern and regulation of the inflammatory process. In conclusion, we found that different doses of acute aerobic exercise induced a distinct and specific c-inflammamiR response, which may be associated with control of the exercise-induced inflammatory cascade. Our findings point to c-inflammamiRs as potential biomarkers of exercise-induced inflammation, and hence, exercise dose.

Contribution of bone turnover markers to bone mass in pubertal boys and girls.

BACKGROUND AND AIMS: The association between bone turnover markers and bone mass in adolescence is not clear. We aimed to evaluate the associations between bone turnover markers and bone mineral content (BMC), density (BMD) and area (BMA). SUBJECTS: A total of 56 adolescents (25 boys, 12.5-17.5 years) participated in the study. METHODS: Bone mass and physical activity (PA) were measured using dual energy X-ray absorptiometry and accelerometers. Osteocalcin and amino-terminal propeptide of type I procollagen (PINP), as markers of bone formation, and beta-isomer of the C-terminal telopeptide of type I collagen, as marker of bone resorption were also measured. Sexual maturation, weight, height and average PA were considered as confounders. RESULTS: Positive correlations (Pearson) were observed among the three bone turnover markers (r = 0.7-0.9). Stepwise multiple linear regression analyses showed that PINP was strong and negatively associated with BMC, BMD and BMA in girls, explaining 24.9% of the variance in BMC, 25.6% in BMD and 16.3% in BMA. CONCLUSION: PINP is a strong predictor of bone related variables in pubertal girls.