Influence of Insufficient Sleep On Circulating microRNAs in Middle‐Aged Adults

Abstract

MicroRNAs (miRs) are short single stranded noncoding RNAs that are involved in regulation of gene expression by inhibiting translation of targeted mRNA transcripts. Cells package and actively secrete miRs into the circulation and the circulating miR signature has been shown to reflect cellular expression. It is well‐recognized that miRs play a key role in regulating vascular health and circulating levels are altered in association with cardiovascular disease (CVD) and represent novel biomarkers of disease and risk. Indeed, altered circulating miR signature has been linked with the development and progression of vascular dysfunction, inflammation and CVD. Habitual short sleep duration (<7 hours/night) is associated with increased morbidity and mortality due, in large part, to increased inflammatory burden and endothelial dysfunction which, in turn, heightens vascular risk. The factors contributing to the increased inflammation and vascular dysfunction associated with habitual short sleep are poorly understood. The aim of this study was to determine whether the circulating expression of inflammation‐ and vascular‐related miRs: miR‐34a; miR‐92a; miR‐125a; miR‐126; miR‐146a; and miR‐150 differ between middle‐aged adults who habitually sleep <7 h/night (short sleep) and those who sleep >7.0 h/night (normal sleep). To address this aim 24 middle‐aged adults were studied: 12 with normal nightly sleep duration (6M/6F; age: 55±3 y; sleep duration: 7.6±0.1 h/night) and 12 with short nightly sleep duration (7M/5F; 55±2 y; 6.0±0.2 h/night). All subjects were non‐smokers, normolipidemic, non‐medicated and free of overt CVD. Women were at least 1 year post‐menopausal and not taking hormone replacement therapy. Circulating miRNA was isolated from plasma and expression was assayed using real time reverse transcription polymerase chain reaction (RT‐PCR). All values were normalized to exogenous C. elegans miR‐39 and reported as relative expression (arbitrary units). Circulating levels of miR‐125a (3.11±0.07 vs 7.32±1.50), miR‐126 (1.56±0.28 vs 2.81±0.50 AU) and miR‐146a (3.33±0.70 vs 8.54±2.20) were significantly lower (~60%, 45% and 65%, respectively) in short compared with the normal sleep group. Circulating levels of miR‐34a, (1.71±0.30 vs 1.67±0.37), miR‐92a (0.71±0.11 vs 0.93±0.22) and miR‐150 (0.9±0.21 vs 1.45±0.40) were not significantly different between the groups. In summary, chronic short sleep is associated with marked alterations in circulating inflammation‐ and vascular‐related miRs. Lower circulating expression of miR‐125a, miR‐126 and miR‐146a is associated with increased vascular inflammation and reduced vasomotor function. Dysregulation of miRs may contribute to the increased inflammatory burden and endothelial dysfunction associated with habitual insufficient sleep.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.