Small RNA-seq during acute maximal exercise reveal RNAs involved in vascular inflammation and cardiometabolic health: brief report

• Published in: American journal of physiology. Heart and circulatory physiology 2017-12, Vol.313 (6), p.H1162-H1167
• Main Authors: Shah, Ravi, Yeri, Ashish, Das, Avash, Courtright-Lim, Amanda, Ziegler, Olivia, Gervino, Ernest, Ocel, Jeffrey, Quintero-Pinzon, Pablo, Wooster, Luke, Bailey, Cole Shields, Tanriverdi, Kahraman, Beaulieu, Lea M, Freedman, Jane E, Ghiran, Ionita, Lewis, Gregory D, Van Keuren-Jensen, Kendall, Das, Saumya
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Bicycles; Bicycling; Cardiovascular disease; Cardiovascular diseases; Circulating MicroRNA - blood; Circulating MicroRNA - genetics; Disease resistance; Exercise; Exercise Test - methods; Female; Gene sequencing; Genetic Markers; Health; Health Status; Humans; Inflammation - blood; Inflammation - diagnosis; Inflammation - genetics; Insulin; Male; Metabolic Syndrome - blood; Metabolic Syndrome - diagnosis; Metabolic Syndrome - genetics; Mice; Mice, Inbred C57BL; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Plasma; Ribonucleic acid; RNA; RNA, Transfer - blood; RNA, Transfer - genetics; Sepsis; Skeletal muscle; Time Factors; Transcription
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00500.2017

Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. We performed plasma small RNA sequencing in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry. We found changes in miRNAs and other ex-RNAs with exercise (e.g., Y RNAs and tRNAs) implicated in cardiovascular disease. In two independent cohorts of acute maximal exercise, we identified miR-181b-5p as a key ex-RNA increased in plasma after exercise, with validation in a separate cohort. In a mouse model of acute exercise, we found significant increases in miR-181b-5p expression in skeletal muscle after acute exercise in young (but not older) mice. Previous work revealed a strong role for miR-181b-5p in vascular inflammation in obesity, insulin resistance, sepsis, and cardiovascular disease. We conclude that circulating ex-RNAs were altered in plasma after acute exercise target pathways involved in inflammation, including miR-181b-5p. Further investigation into the role of known (e.g., miRNA) and novel (e.g., Y RNAs) RNAs is warranted to uncover new mechanisms of vascular inflammation on exercise-mediated benefits on health. How exercise provides benefits to cardiometabolic health remains unclear. We performed RNA sequencing in plasma during exercise to identify the landscape of small noncoding circulating transcriptional changes. Our results suggest a link between inflammation and exercise, providing rich data on circulating noncoding RNAs for future studies by the scientific community.