title: Plasma microRNAs are associated with atrial fibrillation and change after catheter ablation (the miRhythm study).
abstract: BACKGROUND
  MicroRNAs (miRNAs) are associated with cardiovascular disease and control gene expression and are detectable in the circulation.
  
  
  OBJECTIVE
  The purpose of this study was to test the hypothesis that circulating miRNAs may be associated with atrial fibrillation (AF).
  
  
  METHODS
  Using a prospective study design powered to detect subtle differences in miRNAs, we quantified plasma expression of 86 miRNAs by high-throughput quantitative reverse transcriptase-polymerase chain reaction in 112 participants with AF and 99 without AF. To examine parallels between cardiac and plasma miRNA profiles, we quantified atrial tissue and plasma miRNA expression using quantitative reverse transcriptase-polymerase chain reaction in 31 participants undergoing surgery. We also explored the hypothesis that lower AF burden after ablation would be reflected in the circulating blood pool by examining change in plasma miRNAs after AF ablation (n = 47).
  
  
  RESULTS
  Mean age of the cohort was 59 years; 58% of participants were men. Plasma miRs-21 and 150 were 2-fold lower in participants with AF than in those without AF after adjustment (P ≤.0006). Plasma levels of miRs-21 and 150 also were lower in participants with paroxysmal AF than in those with persistent AF (P <.05). Expression of miR-21, but not of miR-150, was lower in atrial tissue from patients with AF than in those without AF (P <.05). Plasma levels of miRs-21 and 150 increased 3-fold after AF ablation (P ≤.0006).
  
  
  CONCLUSIONS
  Cardiac miRs-21 and 150 are known to regulate genes implicated in atrial remodeling. Our findings show associations between plasma miRs-21 and 150 and AF, suggesting that circulating miRNAs can provide insights into cardiac gene regulation.
authors.affiliation: Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Epidemiology Division, Department of Quantitative Health Sciences, University of Massachusetts Medical School Worcester, Massachusetts. Electronic address: mcmanusd@ummhc.org.
authors.forename: David D
authors.initials: DD
authors.lastname: McManus
authors.affiliation: Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Kahraman
authors.initials: K
authors.lastname: Tanriverdi
authors.affiliation: National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Computational Biomedicine Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Honghuang
authors.initials: H
authors.lastname: Lin
authors.affiliation: Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Nada
authors.initials: N
authors.lastname: Esa
authors.affiliation: Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Menhel
authors.initials: M
authors.lastname: Kinno
authors.affiliation: Cardiothoracic Surgery Division, Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Divakar
authors.initials: D
authors.lastname: Mandapati
authors.affiliation: Cardiothoracic Surgery Division, Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Stanley
authors.initials: S
authors.lastname: Tam
authors.affiliation: Cardiothoracic Surgery Division, Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: Okike N
authors.initials: ON
authors.lastname: Okike
authors.affiliation: Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
authors.affiliation: Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: John F
authors.initials: JF
authors.lastname: Keaney
authors.affiliation: Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Donahue
authors.affiliation: National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Epidemiology Department, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Freedman
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000209:etiology / Q000601:surgery*; D016022:Case-Control Studies; D017115:Catheter Ablation; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D035683:MicroRNAs
keywords: Arial fibrillation; Circulation; Epidemiology; MicroRNA; Risk factor