Yu Xue-Jing, Zou Li-Hui, Jin Jun-Hua, Xiao Fei, Li Li, Liu Nan, Yang Jie-Fu, Zou Tong
Department of Cardiology, Peking University Fifth School of Clinical MedicineBeijing 100730, P. R. China.
The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of GerontologyBeijing 100730, P. R. China.
Am J Transl Res. 2017 May 15;9(5):2314-2326. eCollection 2017.
Atrial fibrillation (AF) is a common arrhythmia in clinical practice. Currently, approximately 33.5 million individuals are affected by AF globally. AF involves multiple complicated mechanisms which have not been fully investigated yet. RNA sequencing (RNAseq) is an outstanding method for investigation of diseases due to its high-throughput information. Here, RNAseq was applied to determine mRNA and long noncoding RNA (lncRNA) expression profiles in human lymphocytes from 6 permanent atrial fibrillation (pmAF) patients and 6 healthy controls. Quantitative real-time PCR (qRT-PCR) was applied to further validate 3 lncRNAs and 4 inflammatory mRNAs. It was discovered that there were numerous differentially-expressed mRNAs and lncRNAs between these two groups. GO analysis indicated that differentially-expressed mRNAs were mainly involved in native immunity, inflammation, signaling transduction and so forth, and they were also enriched in pathways like TNF signaling pathway, NF-kappa B signaling pathway, Toll-like receptor pathway and NOD-like receptor pathway. Moreover, co-expression network demonstrated that dysregulated mRNAs and lncRNAs in pmAF lymphocytes participated in inflammation, autophagy, mitochondrial functions, oxidative stress, etc. Further validation by qRT-PCR demonstrated mRNAs and lncRNAs were significantly higher in lymphocytes from pmAF patients compared with controls. In conclusion, mRNA and lncRNA expression profiles in lymphocytes are significantly different between pmAF and controls, differentially-expressed mRNAs and lncRNAs are involved in pathways closely associated with inflammation, oxidative stress, autophagy, cell apoptosis and collagen synthesis, suggesting lymphocytes might play indispensable roles in the development of pmAF.
心房颤动(AF)是临床实践中一种常见的心律失常。目前,全球约有3350万人受AF影响。AF涉及多种复杂机制,尚未得到充分研究。RNA测序(RNAseq)因其高通量信息,是一种出色的疾病研究方法。在此,应用RNAseq来确定6例永久性心房颤动(pmAF)患者和6例健康对照者的人淋巴细胞中的mRNA和长链非编码RNA(lncRNA)表达谱。应用定量实时PCR(qRT-PCR)进一步验证3种lncRNA和4种炎性mRNA。发现这两组之间存在大量差异表达的mRNA和lncRNA。基因本体(GO)分析表明,差异表达的mRNA主要参与天然免疫、炎症、信号转导等,并且它们还富集于肿瘤坏死因子(TNF)信号通路、核因子κB(NF-κB)信号通路、Toll样受体通路和NOD样受体通路等途径。此外,共表达网络表明,pmAF淋巴细胞中失调的mRNA和lncRNA参与炎症、自噬、线粒体功能、氧化应激等。通过qRT-PCR进一步验证表明,与对照组相比,pmAF患者淋巴细胞中的mRNA和lncRNA显著更高。总之,pmAF患者与对照组淋巴细胞中的mRNA和lncRNA表达谱存在显著差异,差异表达的mRNA和lncRNA参与与炎症、氧化应激、自噬、细胞凋亡和胶原蛋白合成密切相关的途径,提示淋巴细胞可能在pmAF的发生发展中发挥不可或缺的作用。