Wahl Patrick, Wehmeier Udo F, Jansen Felix J, Kilian Yvonne, Bloch Wilhelm, Werner Nikos, Mester Joachim, Hilberg Thomas
Institute of Training Science and Sport Informatics, German Sport University CologneCologne, Germany; Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University CologneCologne, Germany; The German Research Centre of Elite Sport, German Sport University CologneCologne, Germany.
Department for Sports Medicine, University of Wuppertal Wuppertal, Germany.
Front Physiol. 2016 Dec 26;7:643. doi: 10.3389/fphys.2016.00643. eCollection 2016.
mircoRNAs (miRNAs), small non-coding RNAs regulating gene expression, are stably secreted into the blood and circulating miRNAs (c-miRNAs) may play an important role in cell-cell communication. Furthermore, c-miRNAs might serve as novel biomarkers of the current vascular cell status. Here, we examined how the levels of three vascular c-miRNAs (c-miR-16, c-miR-21, c-miR-126) are acutely affected by different exercise intensities and volumes. 12 subjects performed 3 different endurance exercise protocols: 1. High-Volume Training (HVT; 130 min at 55% peak power output (PPO); 2. High-Intensity Training (HIT; 4 × 4 min at 95% PPO); 3. Sprint-Interval Training (SIT; 4 × 30 s all-out). c-miRNAs were quantified using quantitative real-time PCR with TaqMan probes at time points pre, 0', 30', 60', and 180' after each intervention. The expression of miR-126 and miR-21 was analyzed , in human coronary artery endothelial cells, human THP-1 monocytes, human platelets, human endothelial microparticles (EMPs) and human vascular smooth muscle cells (VSMCs). To investigate the transfer of miRNAs via EMPs, VSMCs were incubated with EMPs. HVT and SIT revealed large increases on c-miR-21 [1.9-fold by HVT (cohen's = 0.85); 1.5-fold by SIT (cohen's = 0.85)] and c-miR-126 [2.2-fold by SIT (cohen's = 1.06); 1.9-fold by HVT (cohen's = 0.85)] post-exercise compared to pre-values, while HIT revealed only small to moderate changes on c-miRs-21 (cohen's = -0.28) and c-miR-126 (cohen's = 0.53). c-miR-16 was only slightly affected by SIT (1.4-fold; cohen's = 0.57), HVT (1.3-fold; cohen's = 0.61) or HIT (1.1-fold; cohen's = 0.2). Further experiments revealed that miR-126 and miR-21 are mainly of endothelial origin. Importantly, under conditions of endothelial apoptosis, miR-126 and miR-21 are packed from endothelial cells into endothelial microparticles, which were shown to transfer miR-126 into target vascular smooth muscle cells. Taken together, we found that HVT and SIT are associated with the release of endothelial miRNAs into the circulation, which can function as intercellular communication devices regulating vascular biology.
微小RNA（miRNA）是一类调控基因表达的小型非编码RNA，可稳定分泌至血液中，而循环中的miRNA（c-miRNA）可能在细胞间通讯中发挥重要作用。此外，c-miRNA可能是当前血管细胞状态的新型生物标志物。在此，我们研究了三种血管c-miRNA（c-miR-16、c-miR-21、c-miR-126）的水平如何受到不同运动强度和运动量的急性影响。12名受试者进行了3种不同的耐力运动方案：1. 高运动量训练（HVT；以55%峰值功率输出（PPO）进行130分钟）；2. 高强度训练（HIT；以95%PPO进行4×4分钟）；3. 短跑间歇训练（SIT；4×30秒全力冲刺）。在每次干预前、干预后0分钟、30分钟、60分钟和180分钟的时间点，使用带有TaqMan探针的定量实时PCR对c-miRNA进行定量。分析了miR-126和miR-21在人冠状动脉内皮细胞、人THP-1单核细胞、人血小板、人内皮微粒（EMP）和人血管平滑肌细胞（VSMC）中的表达。为了研究miRNA通过EMP的转移，将VSMC与EMP一起孵育。与运动前相比，HVT和SIT显示运动后c-miR-21[HVT增加1.9倍（科恩氏d=0.85）；SIT增加1.5倍（科恩氏d=0.85）]和c-miR-126[SIT增加2.2倍（科恩氏d=1.06）；HVT增加1.9倍（科恩氏d=0.85）]大幅升高，而HIT显示c-miRs-21（科恩氏d=-0.28）和c-miR-126（科恩氏d=0.53）仅有小到中度变化。c-miR-16仅受到SIT（1.4倍；科恩氏d=0.57）、HVT（1.3倍；科恩氏d=0.61）或HIT（1.1倍；科恩氏d=0.2）的轻微影响。进一步实验表明，miR-126和miR-21主要来源于内皮细胞。重要的是，在内皮细胞凋亡的情况下，miR-126和miR-21从内皮细胞包装到内皮微粒中，这些微粒已被证明可将miR-126转移至靶血管平滑肌细胞。综上所述，我们发现HVT和SIT与内皮miRNA释放至循环中有关，这些miRNA可作为调节血管生物学的细胞间通讯装置发挥作用。
