Tran Khanh-Van, Majka Jordan, Sanghai Saket, Sardana Mayank, Lessard Darleen, Milstone Zachary, Tanriverdi Kahraman, Freedman Jane E, Fitzgibbons Timothy P, McManus David
Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States.
Department of Biochemistry and Molecular Biology, Clark University, Worcester, MA, United States.
Front Cardiovasc Med. 2019 Aug 14;6:115. doi: 10.3389/fcvm.2019.00115. eCollection 2019.
Epicardial adipose tissue (EAT) has been linked to incidence and recurrence of atrial fibrillation (AF), but the underlying mechanisms that mediate this association remain unclear. Circulating microRNAs (miRNAs) contribute to the regulation of gene expression in cardiovascular diseases, including AF. Thus, we sought to test the hypothesis that circulating miRNAs relate to burden of EAT. We examined the plasma miRNA profiles of 91 participants from the miRhythm study, an ongoing study examining associations between miRNA and AF. We quantified plasma expression of 86 unique miRNAs commonly expressed in cardiomyocytes using quantitative reverse transcriptase polymerase chain reaction (qPCR). From computed tomography, we used validated methods to quantify the EAT area surrounding the left atrium (LA) and indexed it to body surface area (BSA) to calculate indexed LA EAT (iLAEAT). Participants were divided into tertiles of iLAEAT to identify associations with unique miRNAs. We performed logistic regression analyses adjusting for factors associated with AF to examine relations between iLAEAT and miRNA. We performed further bioinformatics analysis of miRNA predicted target genes to identify potential molecular pathways are regulated by the miRNAs. The mean age of the participants was 59 ± 9, 35% were women, and 97% were Caucasian. Participants in the highest tertile of iLAEAT were more likely to have hypertension, heart failure, and thick posterior walls. In regression analyses, we found that miRNAs 155-5p ( < 0.001) and 302a-3p ( < 0.001) were significantly associated with iLAEAT in patients with AF. The predicted targets of the miRNAs identified were implicated in the regulation of cardiac hypertrophy, adipogenesis, interleukin-8 (IL-8), and nerve growth factor (NGF) signaling. miRNA as well as EAT have previously been linked to AF. Our finding that iLAEAT and miRNAs 155-5p and 302a-3p are associated suggest a possible direct link to between these entities in the development and maintenance of AF. Further research is needed to study causal relationships between these biomarkers.
心外膜脂肪组织（EAT）与心房颤动（AF）的发生率和复发有关，但其介导这种关联的潜在机制仍不清楚。循环微RNA（miRNA）参与心血管疾病（包括AF）中基因表达的调控。因此，我们试图验证循环miRNA与EAT负荷相关的假设。我们检测了miRhythm研究中91名参与者的血浆miRNA谱，该研究正在探讨miRNA与AF之间的关联。我们使用定量逆转录聚合酶链反应（qPCR）对心肌细胞中常见的86种独特miRNA的血浆表达进行定量。通过计算机断层扫描，我们使用经过验证的方法对左心房（LA）周围的EAT面积进行定量，并将其与体表面积（BSA）进行指数化，以计算指数化LA EAT（iLAEAT）。参与者被分为iLAEAT三分位数，以确定与独特miRNA的关联。我们进行了逻辑回归分析，对与AF相关的因素进行调整，以研究iLAEAT与miRNA之间的关系。我们对miRNA预测的靶基因进行了进一步的生物信息学分析，以确定受miRNA调控的潜在分子途径。参与者的平均年龄为59±9岁，35%为女性，97%为白种人。iLAEAT最高三分位数的参与者更有可能患有高血压、心力衰竭和后壁增厚。在回归分析中，我们发现miRNA 155-5p（<0.001）和302a-3p（<0.001）在AF患者中与iLAEAT显著相关。所鉴定的miRNA的预测靶标参与了心脏肥大、脂肪生成、白细胞介素-8（IL-8）和神经生长因子（NGF）信号传导的调控。此前miRNA以及EAT都与AF有关。我们发现iLAEAT与miRNA 155-5p和302a-3p相关，这表明在AF的发生和维持过程中，这些实体之间可能存在直接联系。需要进一步研究来探讨这些生物标志物之间的因果关系。
