Yuan Yue, Han Xuejie, Zhao Xinbo, Zhang Haiyu, Vinograd Asiia, Bi Xin, Duan Xiaoxu, Cao Yukai, Gao Qiang, Song Jia, Sheng Li, Li Yue
Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
Bashkir State Medical University, UFA, Republic Bashkortostan, Russia.
J Transl Int Med. 2024 Mar 21;12(1):106-118. doi: 10.2478/jtim-2023-0129. eCollection 2024 Feb.
Atrial fibrillation (AF) is the most common cardiac arrhythmia with severe clinical sequelae, but its genetic characteristic implicated in pathogenesis has not been completely clarified. Accumulating evidence has indicated that circulating exosomes and their carried cargoes, such as long non-coding RNAs (lncRNAs), involve in the progress of multiple cardiovascular diseases. However, their potential role as clinical biomarkers in AF diagnosis and prognosis remains unknown.
Herein, we conducted the sequence and bioinformatic analysis of circulating exosomes harvested from AF and sinus rhythm patients.
A total of 53 differentially expressed lncRNAs were identified, and a total of 6 significantly changed lncRNAs (fold change > 2.0), including NR0046235, NR003045, NONHSAT167247.1, NONHSAT202361.1, NONHSAT205820.1 and NONHSAT200958.1, were verified by qRT-PCR in 215 participants. Moreover, these circulating exosome lncRNA levels were different between paroxysmal and persistent AF patients, which were dramatically associated with abnormal hemodynamics and atrial diameter. Furthermore, we observed that the area under ROC curve (AUC) of six lncRNAs combination for diagnosis of persistent AF was 80.34%. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment pathway analysis indicated these exosome lncRNAs mainly concerning response to chemokine-chemokine receptor interaction, which induced activated inflammation and structural remodeling. In addition, increased plasma levels of CXCR3 ligands, including CXCL4, CXCL9, CXCL10 and CXCL11, were accumulated in AF patient tissues.
Our study provides the transcriptome profile revealing pattern of circulating exosome lncRNAs in atrial structural remodeling, which bring valuable insights into improving prognosis and therapeutic targets for AF.
心房颤动（AF）是最常见的心律失常，具有严重的临床后果，但其发病机制中的遗传特征尚未完全阐明。越来越多的证据表明，循环外泌体及其携带的物质，如长链非编码RNA（lncRNA），参与多种心血管疾病的进展。然而，它们作为AF诊断和预后临床生物标志物的潜在作用仍然未知。
在此，我们对从AF患者和窦性心律患者收集的循环外泌体进行了测序和生物信息学分析。
共鉴定出53个差异表达的lncRNA，其中6个显著变化的lncRNA（倍数变化>2.0），包括NR0046235、NR003045、NONHSAT167247.1、NONHSAT202361.1、NONHSAT205820.1和NONHSAT200958.1，在215名参与者中通过qRT-PCR得到验证。此外，阵发性和持续性AF患者的这些循环外泌体lncRNA水平不同，这与异常血流动力学和心房直径显著相关。此外，我们观察到，六种lncRNA组合诊断持续性AF的ROC曲线下面积（AUC）为80.34%。基因本体（GO）和京都基因与基因组百科全书（KEGG）富集途径分析表明，这些外泌体lncRNA主要与趋化因子-趋化因子受体相互作用的反应有关，这会诱导炎症激活和结构重塑。此外，AF患者组织中积累了血浆中CXCR3配体（包括CXCL4、CXCL9、CXCL10和CXCL11）水平的升高。
我们的研究提供了转录组图谱，揭示了心房结构重塑中循环外泌体lncRNA的模式，这为改善AF的预后和治疗靶点提供了有价值的见解。
