David D McManus1, Kahraman Tanriverdi2, Honghuang Lin3, Nada Esa2, Menhel Kinno2, Divakar Mandapati4, Stanley Tam4, Okike N Okike4, Patrick T Ellinor5, John F Keaney2, J Kevin Donahue2, Emelia J Benjamin6, Jane E Freedman7. 1. 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. 2. Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts. 3. 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. 4. Cardiothoracic Surgery Division, Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts. 5. Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts. 6. 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. 7. 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.
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). CONCLUSION: 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.
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). CONCLUSION: 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.
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