Abstract 58: Extracellular RNA Response to Acute Exercise

Abstract

The benefits of acute exercise on distant organs (including the neurocognitive system) have been recognized, suggesting existence of biomarkers that mediate exercise benefits in target organs. Extracellular RNAs (ex-RNAs) are RNA molecules stable in circulation, capable of regulating gene expression across multiple target organs at a distance. In 26 individuals without clinical cardiovascular disease (myocardial infarction or heart failure), we performed small non-coding RNA sequencing (RNA-seq) from plasma before and after symptom-limited treadmill exercise, with validation of selected microRNAs (miRNAs) in pulmonary arterial blood from 59 individuals referred for cardiopulmonary exercise testing. Acute exercise produced widespread shifts in the plasma ex-RNA transcriptome, with a host of novel ex-RNA subtypes with unknown function (e.g., yRNAs). miR-181b (involved in silencing of NFkB-mediated inflammation in obesity and vascular disease) was significantly increased at peak exercise (relative to rest) in both our discovery (2.3-fold increase after exercise, P=8.46x10 -11 ) and validation cohort (P=0.02). In a mouse model of acute exercise, we found that skeletal muscle miR-181b expression increased in young but not old mice after exercise, with a corresponding reduction in miR-181b mRNA targets. These results provide the first unbiased demonstration of diversity in ex-RNA release after acute exercise in humans, and suggest anti-inflammatory benefits of acute exercise may be mediated in part by circulating non-coding RNAs.