National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts; Epidemiology Division, Department of Quantitative Health Sciences, University of Massachusetts Medical School Worcester, Massachusetts.
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.
Heart Rhythm. 2014 Apr;11(4):663-9. doi: 10.1016/j.hrthm.2014.01.018. Epub 2014 Jan 18.
MicroRNA (miRNA) expression in atrial tissue has been implicated in pathologic susceptibility to atrial fibrillation (AF). Nevertheless, data on how circulating levels relate to AF are limited.
The purpose of this study was to test the hypothesis that circulating miRNAs are associated with AF.
Among 2445 Framingham Heart Study Offspring participants, we measured the expression of 385 circulating whole blood miRNAs by high-throughput quantitative reverse transcriptase polymerase chain reaction. We related miRNA levels with prevalent and new-onset AF.
Mean age of the cohort was 66.3 ± 8.9 years, and 56% were women; 153 participants had clinically apparent AF at baseline, and 107 developed AF during median follow-up of 5.4 years. miRNA-328 (miR-328) expression was lower among participants with prevalent AF (8.76 cycle threshold) compared to individuals with no AF (7.75 cycle threshold, P <.001). The association between miR-328 and prevalent AF persisted after adjustment for age, sex, and technical covariates (odds ratio 1.21, P = 1.8 × 10(-4)) but was attenuated in analyses adjusting for clinical AF risk factors (odds ratio 1.14, P = .017). In contrast to the associations between miR-328 and prevalent AF, none of the circulating miRNAs were associated with incident AF.
Circulating levels of miR-328, a miRNA known to promote atrial electrical remodeling by reducing L-type Ca(2+) channel density, were associated with prevalent AF. Adjustment for risk factors that promote atrial remodeling, including hypertension, attenuated the association between miR-328 and AF, potentially implicating miR-328 as a potential mediator of atrial remodeling and AF vulnerability.
已有研究表明，心房组织中的 microRNA（miRNA）表达与心房颤动（AF）的病理易感性有关。然而，关于循环水平与 AF 的关系的数据有限。
本研究旨在检验循环 miRNA 与 AF 相关的假说。
在 2445 名弗雷明汉心脏研究后代参与者中，我们通过高通量定量逆转录聚合酶链反应测量了 385 种循环全血 miRNA 的表达。我们将 miRNA 水平与现患和新发 AF 相关联。
队列的平均年龄为 66.3±8.9 岁，其中 56%为女性；153 名参与者在基线时有临床明显的 AF，107 名参与者在中位随访 5.4 年内发生 AF。与无 AF 者相比，现患 AF 者的 miRNA-328（miR-328）表达水平较低（8.76 个循环阈值）（P<0.001）。在调整年龄、性别和技术协变量后，miR-328 与现患 AF 的相关性仍然存在（优势比 1.21，P=1.8×10(-4)），但在调整临床 AF 危险因素后，相关性减弱（优势比 1.14，P=0.017）。与 miR-328 与现患 AF 的相关性相反，没有一种循环 miRNA 与新发 AF 相关。
已知通过降低 L 型 Ca(2+)通道密度促进心房电重构的 miRNA-328 的循环水平与现患 AF 相关。调整促进心房重构的危险因素（包括高血压）后，miR-328 与 AF 的相关性减弱，这可能表明 miR-328 是心房重构和 AF 易感性的潜在介质。
