McManus David D, Tanriverdi Kahraman, Lin Honghuang, Esa Nada, Kinno Menhel, Mandapati Divakar, Tam Stanley, Okike Okike N, Ellinor Patrick T, Keaney John F, Donahue J Kevin, Benjamin Emelia J, Freedman Jane E
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.
Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
Heart Rhythm. 2015 Jan;12(1):3-10. doi: 10.1016/j.hrthm.2014.09.050. Epub 2014 Oct 9.
MicroRNAs (miRNAs) are associated with cardiovascular disease and control gene expression and are detectable in the circulation.
The purpose of this study was to test the hypothesis that circulating miRNAs may be associated with atrial fibrillation (AF).
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).
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).
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.
微小核糖核酸(miRNA)与心血管疾病相关,可调控基因表达,且能在循环系统中检测到。
本研究旨在验证循环miRNA可能与心房颤动(AF)相关这一假说。
采用前瞻性研究设计以检测miRNA的细微差异,我们通过高通量定量逆转录聚合酶链反应对112例AF患者和99例非AF患者的86种miRNA的血浆表达进行了定量。为研究心脏和血浆miRNA谱之间的相似性,我们在31例接受手术的患者中,使用定量逆转录聚合酶链反应对心房组织和血浆miRNA表达进行了定量。我们还通过检查AF消融术后血浆miRNA的变化(n = 47),探讨了消融后AF负荷降低会在循环血池中得到体现这一假说。
该队列的平均年龄为59岁;58%的参与者为男性。调整后,AF患者血浆中的miR-21和150比非AF患者低2倍(P≤0.0006)。阵发性AF患者血浆中miR-21和150的水平也低于持续性AF患者(P<0.05)。AF患者心房组织中miR-21的表达低于非AF患者,但miR-150的表达无此差异(P<0.05)。AF消融术后血浆中miR-21和150的水平增加了3倍(P≤0.0006)。
已知心脏miR-21和150可调控与心房重塑相关的基因。我们的研究结果显示血浆miR-21和150与AF之间存在关联,表明循环miRNA可为心脏基因调控提供见解。