Gene modules and genes associated with postoperative atrial fibrillation: weighted gene co-expression network analysis and circRNA-miRNA-mRNA regulatory network analysis

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Abstract

Background

Atrial fibrillation (AF) is the most common complication in patients undergoing cardiac surgery. However, the pathogenesis of postoperative AF (POAF) is elusive, and research related to this topic is sparse. Our study aimed to identify key gene modules and genes and to conduct a circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory network analysis of POAF on the basis of bioinformatic analysis.

Methods

The GSE143924 and GSE97455 data sets from the Gene Expression Omnibus (GEO) database were analyzed. Weighted gene co-expression network analysis (WGCNA) was used to identify the key gene modules and genes related to POAF. A circRNA-miRNA-mRNA regulatory network was also built according to differential expression analysis. Functional enrichment analysis was further performed according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.

Results

WGCNA identified 2 key gene modules and 44 key genes that were significantly related to POAF. Functional enrichment analysis of these key genes implicated the following important biological processes (BPs): endosomal transport, protein kinase B signaling, and transcription regulation. The circRNA-miRNA-mRNA regulatory network suggested that KLF10 may take critical part in POAF. Moreover, 2 novel circRNAs, hsa_circRNA_001654 and hsa_circRNA_005899, and 2 miRNAs, hsa-miR-19b-3p and hsa-miR-30a-5p, which related with KLF10, were involved in the network.

Conclusions

Our study provides foundational expression profiles following POAF based on WGCNA. The circRNA-miRNA-mRNA network offers insights into the BPs and underlying mechanisms of POAF.

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Most cited references 38

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Biobank-driven genomic discovery yields new insight into atrial fibrillation biology

Michael Boehnke, Ellen M. Schmidt, Gardar Sveinbjörnsson … (2018)

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Postoperative atrial fibrillation: mechanisms, manifestations and management

Dobromir Dobrev, Martín Aguilar, Jordi Heijman … (2019)

Postoperative atrial fibrillation (POAF) complicates 20-40% of cardiac surgical procedures and 10-20% of non-cardiac thoracic operations. Typical features include onset at 2-4 days postoperatively, episodes that are often fleeting and a self-limited time course. Associated adverse consequences of POAF include haemodynamic instability, increased risk of stroke, lengthened hospital and intensive care unit stays and greater costs. Underlying mechanisms are incompletely defined but include intraoperative and postoperative phenomena, such as inflammation, sympathetic activation and cardiac ischaemia, that combine to trigger atrial fibrillation, often in the presence of pre-existing factors, making the atria vulnerable to atrial fibrillation induction and maintenance. A better understanding of the underlying mechanisms might enable the identification of new therapeutic targets. POAF can be prevented by targeting autonomic alterations and inflammation. β-Blocker prophylaxis is the best-established preventive therapy and should be started or continued before cardiac surgery, unless contraindicated. When POAF occurs, rate control usually suffices, and routine rhythm control is unnecessary; rhythm control should be reserved for patients who develop haemodynamic instability or show other indications that rate control alone will be insufficient. In this Review, we summarize the epidemiological and clinical features of POAF, the available pathophysiological evidence from clinical and experimental investigations, the results of prophylactic and therapeutic approaches and the consensus recommendations of various national and international societies.

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Post-operative atrial fibrillation: a maze of mechanisms

Bart Maesen, Jan Nijs, Jos G. Maessen … (2011)

Post-operative atrial fibrillation (POAF) is one of the most frequent complications of cardiac surgery and an important predictor of patient morbidity as well as of prolonged hospitalization. It significantly increases costs for hospitalization. Insights into the pathophysiological factors causing POAF have been provided by both experimental and clinical investigations and show that POAF is ‘multi-factorial’. Facilitating factors in the mechanism of the arrhythmia can be classified as acute factors caused by the surgical intervention and chronic factors related to structural heart disease and ageing of the heart. Furthermore, some proarrhythmic mechanisms specifically occur in the setting of POAF. For example, inflammation and beta-adrenergic activation have been shown to play a prominent role in POAF, while these mechanisms are less important in non-surgical AF. More recently, it has been shown that atrial fibrosis and the presence of an electrophysiological substrate capable of maintaining AF also promote the arrhythmia, indicating that POAF has some proarrhythmic mechanisms in common with other forms of AF. The clinical setting of POAF offers numerous opportunities to study its mechanisms. During cardiac surgery, biopsies can be taken and detailed electrophysiological measurements can be performed. Furthermore, the specific time course of POAF, with the delayed onset and the transient character of the arrhythmia, also provides important insight into its mechanisms. This review discusses the mechanistic interaction between predisposing factors and the electrophysiological mechanisms resulting in POAF and their therapeutic implications.

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Author and article information

Journal

Journal ID (nlm-ta): J Thorac Dis

Journal ID (iso-abbrev): J Thorac Dis

Journal ID (publisher-id): JTD

Title: Journal of Thoracic Disease

Publisher: AME Publishing Company

ISSN (Print): 2072-1439

ISSN (Electronic): 2077-6624

Publication date (Electronic): 26 September 2023

Publication date (Print): 28 September 2023

Volume: 15

Issue: 9

Pages: 4949-4960

Affiliations

[1 ]deptDepartment of Cardiology, Qingdao Municipal Hospital , Qingdao University , Qingdao, China;

[2 ]deptDepartment of Cardiology, Qingdao Municipal Hospital , University of Health and Rehabilitation Sciences , Qingdao, China;

[3 ]deptDepartment of Pulmonary and Critical Care Medicine , University of Health and Rehabilitation Sciences , Qingdao, China;

[4 ]deptDepartment of Cardiovascular Surgery , University of Health and Rehabilitation Sciences , Qingdao, China;

[5 ]deptDepartment of Thoracic and Cardiovascular Surgery, Seoul National University Hospital , Seoul National University College of Medicine , Seoul, Republic of Korea;

[6 ]deptDepartment of Cardiothoracic Surgery , National Heart Centre Singapore , Singapore, Singapore;

[7 ]deptSection of Thoracic Surgery , Dartmouth-Hitchcock Medical Center , 1 Medical Center Dr., Lebanon, NH, USA;

[8 ]deptDepartment of Cardiovascular Surgery , MemorialCare Heart and Vascular Institute , Long Beach, CA, USA

Author notes

Contributions: (I) Conception and design: X Chen, HY Hwang, PYK Pang, JD Phillips, A Khoynezhad; (II) Administrative support: None; (III) Provision of study materials or patients: Z Niu, W Sheng, X Qu; (IV) Collection and assembly of data: X Chen, K Lu, W Han; (V) Data analysis and interpretation: X Chen, H Tang, B Li; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

[#]

These authors contributed equally to this work.

Correspondence to: Bingong Li, MD. Department of Cardiology, Qingdao Municipal Hospital, Qingdao University, No. 1, Jiaozhou Road, Qingdao 266011, China; Department of Cardiology, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, China. Email: libingongqd@ 123456yeah.net ; Wei Han, MD. Department of Pulmonary and Critical Care Medicine, University of Health and Rehabilitation Sciences, No. 1, Jiaozhou Road, Qingdao 266011, China. Email: hanweiqdu@ 123456yeah.net .

Article

Publisher ID: jtd-15-09-4949

DOI: 10.21037/jtd-23-1179

PMC ID: 10586969

PubMed ID: 37868904

SO-VID: 119e514d-194b-4a37-848c-061e3bb9d6a1

License:

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

History

Date received : 28 July 2023

Date accepted : 31 August 2023

Funding

Funded by: the National Natural Science Foundation of China

Award ID: Nos. 81900291 and 82202384

Gene modules and genes associated with postoperative atrial fibrillation: weighted gene co-expression network analysis and circRNA-miRNA-mRNA regulatory network analysis

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Abstract

Background

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Conclusions

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Core Readings in Statistical Mediation Analysis

Most cited references 38

Biobank-driven genomic discovery yields new insight into atrial fibrillation biology

Postoperative atrial fibrillation: mechanisms, manifestations and management

Post-operative atrial fibrillation: a maze of mechanisms

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