Non-technical summary MicroRNA (miRNA) molecules are essential intracellular mediators of numerous biological processes including angiogenesis, inflammation, and mitochondrial metabolism. Recently, it has been shown that miRNAs are secreted into the bloodstream and that circulating miRNAs (c-miRNAs) may serve important endocrine functions. This study examined plasma profiles of specific c-miRNAs in healthy competitive athletes at rest and during exhaustive exercise testing, before and after a 90 day period of exercise training. In this setting, we observed four distinct patterns of c-miRNA response to exercise: (1) c-miRNAs up-regulated by acute exhaustive exercise before and after sustained exercise training, (2) c-miRNAs responsive to acute exhaustive exercise before but not after sustained exercise training, (3) c-miRNAs responsive only to sustained exercise training, and (4) non-responsive c-miRNAs. These findings set the stage for further work aimed at defining the role of c-miRNAs as fitness biomarkers and physiological mediators of exercise-induced cardiovascular adaptation.Abstract MicroRNAs (miRNAs) are intracellular mediators of essential biological functions. Recently, plasma-based 'circulating' miRNAs (c-miRNAs) have been shown to control cellular processes, but the c-miRNA response to human exercise remains unknown. We sought to determine whether c-miRNAs are dynamically regulated in response to acute exhaustive cycling exercise and sustained rowing exercise training using a longitudinal, repeated measures study design. Specifically, c-miRNAs involved in angiogenesis (miR-20a, miR-210, miR-221, miR-222, miR-328), inflammation (miR-21, miR-146a), skeletal and cardiac muscle contractility (miR-21, miR-133a), and hypoxia/ischaemia adaptation (miR-21, miR-146a, and miR-210) were measured at rest and immediately following acute exhaustive cycling exercise in competitive male rowers (n = 10, age = 19.1 ± 0.6 years) before and after a 90 day period of rowing training. Distinct patterns of c-miRNA response to exercise were observed and adhered to four major profiles: (1) c-miRNA up-regulated by acute exercise before and after sustained training (miR-146a and miR-222), (2) c-miRNA responsive to acute exercise before but not after sustained training (miR-21 and miR-221), (3) c-miRNA responsive only to sustained training (miR-20a), and (4) non-responsive c-miRNA (miR-133a, miR-210, miR-328). Linear correlations were observed between peak exercise levels of miR-146a andV O 2 max (r = 0.63, P = 0.003) and between changes in resting miR-20a and changes inV O 2 max (pre-training vs. post-training, r = 0.73; P = 0.02). Although future work is required, these results suggest the potential value of c-miRNAs as exercise biomarkers and their possible roles as physiological mediators of exercise-induced cardiovascular adaptation.
6Li MAS NMR has been used to study the lithium local environments and manganese electronic structures of a number of lithium manganese oxides with manganese oxidation states varying from (III) to (IV). Most samples were chosen with compositions within the LiMn2O4−Li2Mn4O9−Li4Mn5O12 phase diagram, but Li2Mn2O4 with Mn(III) was also synthesized for comparison. Despite the presence of unpaired electrons, high-resolution spectra could still be acquired, allowing a number of different local environments to be detected. Assignments of the resonances to different lithium local environments were made by comparing the observed shifts and local structures in a number of lithium manganates. Two 6Li NMR resonances were observed for the spinel phase Li4Mn5O12 at 1980 and 847 ppm, which were assigned to Li+ in the octahedral and tetrahedral sites of the spinel structure, respectively. A shift was observed for Li+ in the tetrahedral site of Li2Mn4O9, which also contains Mn(IV), at 687 ppm. The shifts are ascribed primarily to a Fermi-contact shift mechanism, and possible mechanisms to account for the directions and sizes of the shift are discussed. Shifts to lower frequency are observed as the manganese oxidation state is reduced (i.e., for manganates containing occupied eg orbitals). The 6Li MAS NMR spectra of the spinels with a Li:Mn ratio of 1:2 are extremely sensitive to the synthesis conditions. When relatively high synthesis temperatures (850 °C) are used, a single resonance at 520 ppm, from the normal spinel phase, dominates. In contrast, several resonances are observed for samples synthesized at lower temperatures (550−650 °C), as a result of defects in the normal spinel structure. These resonances collapse into the main spinel resonance at high temperatures (250 °C) and are assigned to electronic defects associated with higher oxidation state manganese ions (Mn4+). No evidence for a Jahn−Teller distortion is observed in both the NMR and by diffraction for samples that contain considerable disorder. In contrast, samples that were prepared at temperatures of 650 °C or higher show a cubic-to-tetragonal phase change below room temperature. This is accompanied by the appearance of at least three additional 6Li resonances, indicating some ordering of the Mn3+ and Mn4+ cations below the phase transition, in the time scale of the NMR experiment.
This prospective, longitudinal study examined the effects of participation in team-based exercise training on cardiac structure and function. Competitive endurance athletes (EA, n = 40) and strength athletes (SA, n = 24) were studied with echocardiography at baseline and after 90 days of team training. Left ventricular (LV) mass increased by 11% in EA (116 +/- 18 vs. 130 +/- 19 g/m(2); P < 0.001) and by 12% in SA (115 +/- 14 vs. 132 +/- 11 g/m(2); P < 0.001; P value for the compared Delta = NS). EA experienced LV dilation (end-diastolic volume: 66.6 +/- 10.0 vs. 74.7 +/- 9.8 ml/m(2), Delta = 8.0 +/- 4.2 ml/m(2); P < 0.001), enhanced diastolic function (lateral E': 10.9 +/- 0.8 vs. 12.4 +/- 0.9 cm/s, P < 0.001), and biatrial enlargement, while SA experience LV hypertrophy (posterior wall: 4.5 +/- 0.5 vs. 5.2 +/- 0.5 mm/m(2), P < 0.001) and diminished diastolic function (E' basal lateral LV: 11.6 +/- 1.3 vs. 10.2 +/- 1.4 cm/s, P < 0.001). Further, EA experienced right ventricular (RV) dilation (end-diastolic area: 1,460 +/- 220 vs. 1,650 +/- 200 mm/m(2), P < 0.001) coupled with enhanced systolic and diastolic function (E' basal RV: 10.3 +/- 1.5 vs. 11.4 +/- 1.7 cm/s, P < 0.001), while SA had no change in RV parameters. We conclude that participation in 90 days of competitive athletics produces significant training-specific changes in cardiac structure and function. EA develop biventricular dilation with enhanced diastolic function, while SA develop isolated, concentric left ventricular hypertrophy with diminished diastolic relaxation.
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