title: Rapid upregulation and clearance of distinct circulating microRNAs after prolonged aerobic exercise.
abstract: Short nonprotein coding RNA molecules, known as microRNAs (miRNAs), are intracellular mediators of adaptive processes, including muscle hypertrophy, contractile force generation, and inflammation. During basal conditions and tissue injury, miRNAs are released into the bloodstream as "circulating" miRNAs (c-miRNAs). To date, the impact of extended-duration, submaximal aerobic exercise on plasma concentrations of c-miRNAs remains incompletely characterized. We hypothesized that specific c-miRNAs are differentially upregulated following prolonged aerobic exercise. To test this hypothesis, we measured concentrations of c-miRNAs enriched in muscle (miR-1, miR-133a, miR-499-5p), cardiac tissue (miR-208a), and the vascular endothelium (miR-126), as well as those important in inflammation (miR-146a) in healthy male marathon runners (N = 21) at rest, immediately after a marathon (42-km foot race), and 24 h after the race. In addition, we compared c-miRNA profiles to those of conventional protein biomarkers reflective of skeletal muscle damage, cardiac stress and necrosis, and systemic inflammation. Candidate c-miRNAs increased immediately after the marathon and declined to prerace levels or lower after 24 h of race completion. However, the magnitude of change for each c-miRNA differed, even when originating from the same tissue type. In contrast, traditional biomarkers increased after exercise but remained elevated 24 h postexercise. Thus c-miRNAs respond differentially to prolonged exercise, suggesting the existence of specific mechanisms of c-miRNA release and clearance not fully explained by generalized cellular injury. Furthermore, c-miRNA expression patterns differ in a temporal fashion from corollary conventional tissue-specific biomarkers, emphasizing the potential of c-miRNAs as unique, real-time markers of exercise-induced tissue adaptation.
authors.affiliation: Cardiovascular Performance Program, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Baggish
authors.forename: Joseph
authors.initials: J
authors.lastname: Park
authors.forename: Pil-Ki
authors.initials: PK
authors.lastname: Min
authors.forename: Stephanie
authors.initials: S
authors.lastname: Isaacs
authors.forename: Beth A
authors.initials: BA
authors.lastname: Parker
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thompson
authors.forename: Chris
authors.initials: C
authors.lastname: Troyanos
authors.forename: Pierre
authors.initials: P
authors.lastname: D'Hemecourt
authors.forename: Sophia
authors.initials: S
authors.lastname: Dyer
authors.forename: Marissa
authors.initials: M
authors.lastname: Thiel
authors.forename: Andrew
authors.initials: A
authors.lastname: Hale
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Chan
mesh_terms: D000328:Adult; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010807:Physical Endurance / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D012146:Rest / Q000502:physiology; D012420:Running / Q000502:physiology; D013312:Stress, Physiological; D014336:Troponin / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D010446:Peptide Fragments; D014336:Troponin; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; D003402:Creatine Kinase
keywords: cardiorespiratory fitness biomarker; cardiovascular biomarker; circulating microRNA; exercise physiology; prolonged aerobic exercise