Circulating exosome long non-coding RNAs are associated with atrial structural remodeling by increasing systemic inflammation in atrial fibrillation patients

Yue Yuan; Xuejie Han; Xinbo Zhao; Haiyu Zhang; Asiia Vinograd; Xin Bi; Xiaoxu Duan; Yukai Cao; Qiang Gao; Jia Song; Li Sheng; Yue Li

doi:10.2478/jtim-2023-0129

Circulating exosome long non-coding RNAs are associated with atrial structural remodeling by increasing systemic inflammation in atrial fibrillation patients

J Transl Int Med. 2024 Mar 21;12(1):106-118. doi: 10.2478/jtim-2023-0129. eCollection 2024 Feb.

Authors

Yue Yuan¹, Xuejie Han¹, Xinbo Zhao¹, Haiyu Zhang¹, Asiia Vinograd^{1

2}, Xin Bi¹, Xiaoxu Duan¹, Yukai Cao¹, Qiang Gao¹, Jia Song³, Li Sheng¹, Yue Li^{1

4

5

6

7}

Affiliations

¹ Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
² Bashkir State Medical University, UFA, Republic Bashkortostan, Russia.
³ Department of Medicine, Division of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, Houston 77054, USA.
⁴ NHC Key Laboratory of Cell Transplantation, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
⁵ Key Laboratory of Hepatosplenic Surgery, Harbin Medical University, Ministry of Education, Harbin 150001, Heilongjiang Province, China.
⁶ Heilongjiang Key Laboratory for Metabolic Disorder & Cancer Related Cardiovascular Diseases, Harbin 150081, Heilongjiang Province, China.
⁷ Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.

Abstract

Background: 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.

Methods: Herein, we conducted the sequence and bioinformatic analysis of circulating exosomes harvested from AF and sinus rhythm patients.

Results: 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.

Conclusion: 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.

Keywords: atrial fibrillation; exosomes; inflammation; lncRNAs; structural remodeling.

© 2024 Yue Yuan, Xuejie Han, Xinbo Zhao, Haiyu Zhang, Asiia Vinograd, Xin Bi, Xiaoxu Duan, Yukai Cao, Qiang Gao, Jia Song, Li Sheng, Yue Li, published by De Gruyter on behalf of Scholar Media Publishing.

Grants and funding

This work was supported by the grants from National Natural Science Foundation of China (No.81900302, No.81830012 and No.82070336) and the China Postdoctoral Science Foundation (2018M641869) and the Heilongjiang Providence Postdoctoral Science Foundation (LBH-Z18220). Yue Yuan also has the Excellent Young Medical Talents supporting project in the First Affiliated Hospital of Harbin Medical University (No. HYD2020YQ0001).