Differential MicroRNA expression following head-down tilt bed rest: implications for cardiovascular responses to microgravity

Abstract

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 CO2 of 0.5% (replicate the in-flight CO2 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 ((Formula presented.)) 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. (Formula presented.) 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.