MicroRNAs (miRNAs) are short, noncoding RNAs that influence biological processes by regulating gene expression after transcription. It was recently discovered that miRNAs are released into the circulation (ci-miRNAs) where they are highly stable and can act as intercellular messengers to affect physiological processes. This review provides a comprehensive summary of the studies to date that have investigated the effects of acute exercise and exercise training on ci-miRNAs in humans. Findings indicate that specific ci-miRNAs are altered in response to different protocols of acute and chronic exercise in both healthy and diseased populations. In some cases, altered ci-miRNAs correlate with fitness and health parameters, suggesting causal mechanisms by which ci-miRNAs may facilitate adaptations to exercise training. However, strong data supporting such mechanisms are lacking. Thus, a purpose of this review is to guide future studies by discussing current and novel proposed roles for ci-miRNAs in adaptations to exercise training. In addition, substantial, fundamental gaps in the field need to be addressed. The ultimate goal of this research is that an understanding of the roles of ci-miRNAs in physiological adaptations to exercise training will one day translate to therapeutic interventions.
Endothelial function typically exhibits a hormetic response to exercise. It is unknown whether endothelial damage occurs in response to acute exercise and could be a contributing mechanism. We sought to determine the effects of acute exercise on endothelial-derived circulating factors proposed to reflect endothelial integrity and activation. Young, healthy men ( n = 10) underwent 30-min moderate continuous (MOD) and high-intensity interval (HII) cycling exercise bouts. Venous blood samples were taken immediately before and after exercise for quantification of circulating endothelial cells (CECs), circulating angiogenic cells (CACs), apoptotic and activated endothelial microvesicles (EMVs), thrombomodulin (TM), von Willebrand factor (vWF), syndecan-1, and circulating microRNAs (ci-miRs) 126–3p and 126–5p. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery before, 10 min after, and 60 min after exercise. Numbers of CECs and EMVs were unchanged by either exercise bout ( P > 0.05). Numbers of all measured CAC subtypes decreased in response to MOD (21%–34%, P < 0.05), whereas only CD31+/34+/45dim/− CACs decreased following HII (21%, P < 0.05). TM and syndecan-1 increased with both exercise intensities (both ~20%, P < 0.05). HII, but not MOD, increased vWF (88%, P < 0.001), ci-miR-126–3p (92%, P = 0.009) and ci-miR-126–5p (110%, P = 0.01). The changes in several circulating factors correlated with changes in FMD following either one or both intensities. Changes in circulating factors do not support the concept of exercise-induced endothelial cell denudation, apoptosis, or activation, though slight disruption of endothelial glycocalyx and membrane integrity may occur. A related loss of mechanotransduction along with mechanisms underlying endothelial activation and ci-miR-126 secretion may relate to changes in endothelial function. NEW & NOTEWORTHY Using circulating endothelial-derived factors, we show that endothelial denudation, apoptosis, and activation do not appear to increase, whereas disrupted endothelial glycocalyx and membrane integrity may occur during both high-intensity interval and moderate intensity cycling. Increases in factors nonspecific to endothelial damage, including von Willebrand factor and microRNA-126, occurred only after high-intensity interval exercise. These results shed light on the hypothesis that disrupted endothelial integrity contributes to the endothelial function response to exercise.
We aimed to determine if chronic endurance-exercise habits affected redox status and paracrine function of CD34(+) and CD34(-)/CD31(+) circulating angiogenic cells (CACs). Subjects were healthy, nonsmoking men and women aged 18-35 yr and categorized by chronic physical activity habits. Blood was drawn from each subject for isolation and culture of CD34(+) and CD34(-)/CD31(+) CACs. No differences in redox status were found in any group across either cell type. Conditioned media (CM) was generated from the cultured CACs and used in an in vitro human umbilical vein endothelial cell-based tube assay. CM from CD34(+) cells from inactive individuals resulted in tube structures that were 29% shorter in length (P < 0.05) and 45% less complex (P < 0.05) than the endurance-trained group. CD34(-)/CD31(+) CM from inactive subjects resulted in tube structures that were 26% shorter in length (P < 0.05) and 42% less complex (P < 0.05) than endurance-trained individuals. Proteomics analyses identified S100A8 and S100A9 in the CM. S100A9 levels were 103% higher (P < 0.05) and S100A8 was 97% higher in the CD34(-)/CD31(+) CM of inactive subjects compared with their endurance-trained counterparts with no significant differences in either protein in the CM of CD34(+) CACs as a function of training status. Recombinant S100A8/A9 treatment at concentrations detected in inactive subjects' CD34(-)/CD31(+) CAC CM also reduced tube formation (P < 0.05). These findings are the first, to our knowledge, to demonstrate a differential paracrine role in CD34(+) and CD34(-)/CD31(+) CACs on tube formation as a function of chronic physical activity habits and identifies a differential secretion of S100A9 by CD34(-)/CD31(+) CACs due to habitual exercise.
Current trends suggest professional soccer is becoming less aggressive, with England often argued to have the most aggressive of the top European leagues. The purpose of this study was to investigate differences in fouls and cards as indicators of aggressive play in the first divisions of England, France, Germany, Italy, and Spain over the past decade. Number of fouls per match and per yellow card has decreased in all leagues since 2007/08, though attempted tackles per foul has not changed or has increased. A lack of substantial rule changes suggests players have become less aggressive in tackling as opposed to referees becoming more lenient. Total number of fouls and cards per match were consistently lower in the English Premier League, however attempted tackles per foul was higher. The data also demonstrate the notions of home advantage and potentially referee bias, since referees tended to call more fouls and award more cards to away teams. Lastly, number of attempted tackles per foul and yellow cards received exhibited the strongest correlations with final league position across the leagues. In conclusion, our data support that elite European soccer has become less aggressive and the English Premier League is the most aggressive league.
The beneficial effects of physical activity on brain health (synaptogenesis, neurogenesis, enhanced synaptic plasticity, improved learning and memory) appear to be mediated through changes in region-specific expression of neurotrophins, transcription factors, and postsynaptic receptors, though investigations of sex differences in response to long-term voluntary wheel running are limited. Purpose To examine the effect of five months of voluntary wheel running on hippocampal mRNA and protein expression of factors critical for exercise-induced structural and functional plasticity in male and female adult mice. Methods At 8 weeks of age, male and female C57BL/6 mice were individually housed with (PA; n=20; 10 male) or without (SED; n=20; 10 male) access to a computer monitored voluntary running wheel. At 28 weeks, all mice were sacrificed and hippocampi removed. Total RNA was isolated from the hippocampus and expression of total Bdnf, Bdnf transcript IV, tPA, Pgc-1a, GluR1, NR2A, and NR2B were assessed with quantitative RT-PCR and total and mature Bdnf protein were assessed with ELISA. Results We found significantly higher Bdnf IV mRNA expression in PA males (p=0.03) and females (p=0.03) compared to SED animals. Total Bdnf mRNA expression was significantly greater in PA males compared to SED males (p=0.01), but there was no difference in females. Similarly, we observed significantly higher mature Bdnf protein in PA males compared to SED males (p=0.04), but not in females. Conclusion These findings indicate that the impact of long-term voluntary wheel running on transcriptional and post-translational regulation of Bdnf may be sex-dependent, though the activity-dependent Bdnf IV transcript is sensitive to exercise independent of sex.
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