Differential Circulating microRNA Expression after Bed Rest: Potential Role in Cardiovascular Deconditioning

Abstract

Bed rest, an analog of spaceflight microgravity, elicits changes in left ventricular loading conditions resulting in cardiac deconditioning that adversely effects functional outcomes and cardiopulmonary exercise performance. Given the significant and time‐dependent changes in cardiovascular function associated with bed rest, a continued evaluation of these adaptations are required, particularly in regards to their molecular regulators. MicroRNAs are noncoding RNA that regulate gene expression, with several plasma‐based ‘circulating’ microRNAs (c‐miRs) used as biomarkers of tissue‐specific physiologic adaptation. Quantification of cardiac‐c‐miRs may allow for manifestations of cardiovascular deconditioning to be identified and be used to predict cardiovascular related outcomes in response to bed rest. Therefore, the primary aim of this study was to test the hypotheses that cardiovascular‐c‐miRs are differentially expressed following bed rest and their changes associated with decreases in cardiac function and cardiopulmonary exercise capacity. Eleven participants completed 30‐days bed rest at an ambient CO2 of 0.05% (replicate CO2 levels on the International Space Station). Blood samples were obtained prior to and immediately following bed rest. 44‐targeted c‐miRs identified from published roles in cardiovascular structure/function were analyzed via RT‐qPCR. Resting stroke volume was evaluated via ultrasonography. Peak oxygen uptake (peakVO2) was determined using a grade exercise test. Ten cardiovascular‐c‐miRs were significantly increased following bed rest. The differentially expressed c‐miRs were grouped into clusters according to their expression profile. Cluster A included c‐miRs that have been identified as regulators of cardiac function and hypertrophy (c‐miR‐133), atrial fibrillation and mitochondrial function (c‐miR‐1), skeletal muscle atrophy (c‐miR‐1), vascular control (c‐miR‐155) and aerobic capacity (c‐miR‐133). Cluster B contained c‐miR identified as regulators of cardiac hypertrophy (c‐miR‐30, c‐miR‐15), fibrosis (c‐miR‐22, c‐miR‐18), mitochondrial function (c‐miR‐181), and aerobic capacity (c‐miR‐20a). Following bed rest stroke volume was decreased and correlated with changes in cmiR‐18a and c‐miR‐378a. PeakVO2 was decreased and correlated with changes in c‐miR‐133. In conclusion, we found that bed rest induced a distinct and specific cardiovascular‐c‐miR response, which was associated with changes in cardiac function and cardiopulmonary exercise capacity. Although future work is required, these results suggest the potential value of c‐miRs as biomarkers and their possible role as physiological mediators of cardiovascular deconditioning to bed rest.Support or Funding InformationNational Aeronautics and Space Administration (NASA) research grant awarded to C.J AdeThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.