Immune remodeling and atrial fibrillation

Yao, Yajun; Yang, Mei; Liu, Dishiwen; Zhao, Qingyan

doi:10.3389/fphys.2022.927221

Cited by 27 publications

(33 citation statements)

References 130 publications

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“…Recent studies have shown that considerable changes in the immune system occur during AF, including the recruitment and activation of immune cells and the secretion of their immune molecules induced by various factors; this is a process called immune remodeling (33). Immune remodeling runs through the entire process of the occurrence and maintenance of AF.…”

Section: Discussionmentioning

confidence: 99%

Causal association of peripheral immune cell counts and atrial fibrillation: A Mendelian randomization study

Feng

Liu

2023

Front. Cardiovasc. Med.

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BackgroundAtrial fibrillation (AF) is the most common and persistent form of arrhythmia. Recently, increasing evidence has shown a link between immune responses and atrial fibrillation. However, whether the immune response is a cause or consequence of AF remains unknown. We aimed to determine whether genetically predicted peripheral immunity might have a causal effect on AF.MethodsFirst, we performed Mendelian randomization (MR) analyses using genetic variants strongly associated with neutrophil, eosinophil, basophil, lymphocyte, and monocyte cell counts as instrumental variables (IVs). Lymphocyte counts were then subjected to further subgroup analysis. The effect of immune cell counts on AF risk was measured using summary statistics from genome-wide association studies (GWAS).ResultsTwo-sample MR analysis revealed that a higher neutrophil count, basophil count and lymphocyte count had a causal effect on AF [Odds ratio (OR), 1.06, 95% confidence interval (CI), 1.01–1.10, P = 0.0070; OR, 1.10; 95% CI, 1.04–1.17; P = 0.0015; OR, 0.96; 95% CI, 0.93–0.99; P = 0.0359]. In addition, in our further analysis, genetically predicted increases in CD4 + T-cell counts were also associated with an increased risk of AF (OR, 1.04; 95% CI, 1.0–.09; P = 0.0493).ConclusionOur MR analysis provided evidence of a genetically predicted causal relationship between higher peripheral immune cell counts and AF. Subgroup analysis revealed the key role of peripheral lymphocytes in AF, especially the causal relationship between CD4 + T cell count and AF. These findings are beneficial for future exploration of the mechanism of AF.

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Section: Discussionmentioning

confidence: 99%

Causal association of peripheral immune cell counts and atrial fibrillation: A Mendelian randomization study

Feng

Liu

2023

Front. Cardiovasc. Med.

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“…It is generally believed that COPD-induced structural changes in the heart, increased sympathetic activity, and hypoxia-induced oxidative stress accelerates the development of AF. But recent studies have highlighted the role of immune dysfunction in the pathogenesis of both diseases, finding that immune dysfunction may play a prominent role in the subsequent inflammatory response, cardiac remodeling, structural remodeling, and neural remodeling ( 11 , 38 ). However, the exact mechanisms have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Combining bioinformatics and machine learning to identify common mechanisms and biomarkers of chronic obstructive pulmonary disease and atrial fibrillation

Sun

Lin

Zhang

et al. 2023

Front. Cardiovasc. Med.

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BackgroundPatients with chronic obstructive pulmonary disease (COPD) often present with atrial fibrillation (AF), but the common pathophysiological mechanisms between the two are unclear. This study aimed to investigate the common biological mechanisms of COPD and AF and to search for important biomarkers through bioinformatic analysis of public RNA sequencing databases.MethodsFour datasets of COPD and AF were downloaded from the Gene Expression Omnibus (GEO) database. The overlapping genes common to both diseases were screened by WGCNA analysis, followed by protein-protein interaction network construction and functional enrichment analysis to elucidate the common mechanisms of COPD and AF. Machine learning algorithms were also used to identify key biomarkers. Co-expression analysis, “transcription factor (TF)-mRNA-microRNA (miRNA)” regulatory networks and drug prediction were performed for key biomarkers. Finally, immune cell infiltration analysis was performed to evaluate further the immune cell changes in the COPD dataset and the correlation between key biomarkers and immune cells.ResultsA total of 133 overlapping genes for COPD and AF were obtained, and the enrichment was mainly focused on pathways associated with the inflammatory immune response. A key biomarker, cyclin dependent kinase 8 (CDK8), was identified through screening by machine learning algorithms and validated in the validation dataset. Twenty potential drugs capable of targeting CDK8 were obtained. Immune cell infiltration analysis revealed the presence of multiple immune cell dysregulation in COPD. Correlation analysis showed that CDK8 expression was significantly associated with CD8+ T cells, resting dendritic cell, macrophage M2, and monocytes.ConclusionsThis study highlights the role of the inflammatory immune response in COPD combined with AF. The prominent link between CDK8 and the inflammatory immune response and its characteristic of not affecting the basal expression level of nuclear factor kappa B (NF-kB) make it a possible promising therapeutic target for COPD combined with AF.

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“…These mechanisms lead to increased ectopic atrial activity as well as slow and heterogenous atrial conduction resulting in abnormal atrial depolarizations and the promotion of re-entry circuits [18]. Additionally, systemic inflammation induces endocardial and endothelial inflammation facilitating atrial remodeling [18]. Various inflammatory mediators are implicated in these processes including TNF-α, IL-2, and platelet-derived growth factor (PDGF) [6,11].…”

Section: Contemporary Pathophysiology Of Atrial Fibrillation In the C...mentioning

confidence: 99%

Inflammatory bowel disease and atrial fibrillation: a contemporary overview

Konstantinou¹,

Korantzopoulos²,

Fousekis

et al. 2023

European Journal of Gastroenterology &Amp; Hepatology

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Atrial fibrillation is the most common arrhythmia in clinical practice and it is associated with increased morbidity and mortality. Atrial fibrillation is linked with inflammatory signaling while inflammation and oxidative stress promote atrial remodeling promoting the development and perpetuation of the arrhythmia. On the other hand, inflammatory bowel disease (IBD) is considered a chronic inflammatory condition with flares and remissions. IBD has been associated with an increased risk of atherosclerotic cardiovascular disease but its relationship with atrial fibrillation has not been studied well. Recent epidemiological evidence indicates an association between IBD and atrial fibrillation, especially during flares/hospitalizations. This brief review provides a concise overview of all available data regarding the association between IBD and atrial fibrillation including the predictive role of electrocardiographic and echocardiographic markers. Several unresolved issues including the thromboembolic risk in this setting and the potential role of antiinflammatory interventions are also discussed.

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Immune remodeling and atrial fibrillation

Cited by 27 publications

References 130 publications

Causal association of peripheral immune cell counts and atrial fibrillation: A Mendelian randomization study

Causal association of peripheral immune cell counts and atrial fibrillation: A Mendelian randomization study

Combining bioinformatics and machine learning to identify common mechanisms and biomarkers of chronic obstructive pulmonary disease and atrial fibrillation

Inflammatory bowel disease and atrial fibrillation: a contemporary overview

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