Ade Carl J, Bemben Debra A
Department of Kinesiology, Kansas State University, Manhattan, Kansas.
Department of Health and Exercise Science, University of Oklahoma, Norman, Oklahoma.
Physiol Rep. 2019 May;7(9):e14061. doi: 10.14814/phy2.14061.
Head-down tilt bedrest (HDBR), an analog of spaceflight, elicits changes in cardiovascular function that adversely affect astronaut performance. It is therefore fundamental to elucidate the molecular regulators of these changes. Study aim was to determine if cardiovascular-related circulating microRNA (miRNA) are altered following HDBR and if they relate to changes in cardiac function and peak aerobic capacity. Eleven participants completed 30-days HDBR at an ambient CO of 0.5% (replicate the in-flight CO levels). Blood samples were obtained 3 days (BDC-3) prior to and immediately (R + 0) following HDBR. 44-targeted circulating miRNAs (c-miRNA) identified from published roles in cardiovascular structure/function were analyzed via RT-qPCR. Resting stroke volume was evaluated via ultrasonography. Peak oxygen uptake ( ) was determined using a graded exercise test on an electronically braked cycle ergometer. Ten cardiovascular-related miRNA were significantly increased following HDBR. The differentially expressed c-miRNA were grouped into clusters according to their expression profile. Cluster A included c-miRNA that have been identified as regulators of cardiac function and hypertrophy (c-miRNA-133), atrial fibrillation and mitochondrial function (c-miRNA-1), skeletal muscle atrophy (c-miRNA-1), and vascular control (c-miRNA-155). Cluster B contained c-miRNA identified as regulators of cardiac hypertrophy (c-miRNA-30, -15), fibrosis (c-miRNA-22, -18), mitochondrial function (miRNA-181), and aerobic capacity (c-miRNA-20a). Following HDBR resting stroke volume was decreased and correlated with changes in c-miRNA-378a and -18a. was decreased and correlated with changes c-miRNA-133. In conclusion, we found that HDBR induced a distinct and specific cardiovascular-related miRNA response, which were associated with changes in cardiac function and peak aerobic capacity.
头低位卧床休息（HDBR）是太空飞行的模拟状态，会引发心血管功能变化，对宇航员的表现产生不利影响。因此，阐明这些变化的分子调节因子至关重要。研究目的是确定HDBR后心血管相关循环微RNA（miRNA）是否发生改变，以及它们是否与心脏功能和最大有氧能力的变化有关。11名参与者在环境二氧化碳浓度为0.5%的条件下完成了30天的HDBR（模拟飞行中的二氧化碳水平）。在HDBR前3天（BDC - 3）和之后立即（R + 0）采集血样。通过逆转录定量聚合酶链反应（RT - qPCR）分析从已发表的心血管结构/功能作用中鉴定出的44种靶向循环miRNA（c - miRNA）。通过超声心动图评估静息每搏输出量。使用电子刹车的自行车测力计进行分级运动试验来测定最大摄氧量（ ）。HDBR后，10种心血管相关miRNA显著增加。差异表达的c - miRNA根据其表达谱分组。A组包括已被确定为心脏功能和肥大调节因子（c - miRNA - 133）、心房颤动和线粒体功能调节因子（c - miRNA - 1）、骨骼肌萎缩调节因子（c - miRNA - 1）以及血管控制调节因子（c - miRNA - 155）的c - miRNA。B组包含已被确定为心脏肥大调节因子（c - miRNA - 30、- 15）、纤维化调节因子（c - miRNA - 22、- 18）、线粒体功能调节因子（miRNA - 181）以及有氧能力调节因子（c - miRNA - 20a）的c - miRNA。HDBR后静息每搏输出量降低，并与c - miRNA - 378a和 - 18a的变化相关。 降低，并与c - miRNA - 133的变化相关。总之，我们发现HDBR诱导了一种独特且特定的心血管相关miRNA反应，这与心脏功能和最大有氧能力的变化有关。
