Circulating proteomic patterns in AF related left atrial remodeling indicate involvement of coagulation and complement cascade

Kornej, Jelena; Büttner, Petra; Hammer, Elke; Engelmann, Beatrice; Dinov, Borislav; Sommer, Philipp; Husser, Daniela; Hindricks, Gerhard; Völker, Uwe; Bollmann, Andreas

doi:10.1101/327759

Cited by 3 publications

(1 citation statement)

References 32 publications

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“…However, different studies have described contrasting results regarding the effects of the complement system in AF (60). A recent proteomics study demonstrated that left atrial low voltage areas (LVA) in patients with AF, which corresponded to areas of fibrotic and electrically silent myocardial tissue, were associated with an imbalance in coagulation and complement pathways, and complement and coagulation molecules were differentially expressed, including downregulation of C1q-B, C1q-C, CFH and plasminogen compared with patients without LVA (61). ECM dysregulation caused atrial fibrotic remodeling in AF through inflammation and oxidative stress (62), and studies have identified that ECM-associated genes are differentially expressed, with notable differences in gene expression between LA and RA in AF (14,63).…”

Section: Discussionmentioning

confidence: 99%

Weighted gene co‑expression network analysis to identify key modules and hub genes associated with atrial fibrillation

Wang

et al. 2019

Int J Mol Med

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Atrial fibrillation (AF) is the most common form of cardiac arrhythmia and significantly increases the risks of morbidity, mortality and health care expenditure; however, treatment for AF remains unsatisfactory due to the complicated and incompletely understood underlying mechanisms. In the present study, weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and hub genes to determine their potential associations with AF. WGCNA was performed in an AF dataset GSE79768 obtained from the Gene Expression Omnibus, which contained data from paired left and right atria in cardiac patients with persistent AF or sinus rhythm. Differentially expressed gene (DEG) analysis was used to supplement and validate the results of WGCNA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were also performed. Green and magenta modules were identified as the most critical modules associated with AF, from which 6 hub genes, acetyl-CoA Acetyltransferase 1, death domain-containing protein CRADD, gypsy retrotransposon integrase 1, FTX transcript, XIST regulator, transcription elongation factor A like 2 and minichromosome maintenance complex component 3 associated protein, were hypothesized to serve key roles in the pathophysiology of AF due to their increased intramodular connectivity. Functional enrichment analysis results demonstrated that the green module was associated with energy metabolism, and the magenta module may be associated with the Hippo pathway and contain multiple interactive pathways associated with apoptosis and inflammation. In addition, the blue module was identified to be an important regulatory module in AF with a higher specificity for the left atria, the genes of which were primarily correlated with complement, coagulation and extracellular matrix formation. These results suggest that may improve understanding of the underlying mechanisms of AF, and assist in identifying biomarkers and potential therapeutic targets for treating patients with AF.

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Section: Discussionmentioning

confidence: 99%

Weighted gene co‑expression network analysis to identify key modules and hub genes associated with atrial fibrillation

Wang

et al. 2019

Int J Mol Med

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Beyond the Rhythm: In Silico Identification of Key Genes and Therapeutic Targets in Atrial Fibrillation

Atzemian,

Dovrolis,

Ragia

et al. 2023

Biomedicines

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Atrial fibrillation (AF) is a prevalent cardiac arrhythmia worldwide and is characterized by a high risk of thromboembolism, ischemic stroke, and fatality. The precise molecular mechanisms of AF pathogenesis remain unclear. The purpose of this study was to use bioinformatics tools to identify novel key genes in AF, provide deeper insights into the molecular pathogenesis of AF, and uncover potential therapeutic targets. Four publicly available raw RNA-Seq datasets obtained through the ENA Browser, as well as proteomic analysis results, both derived from atrial tissues, were used in this analysis. Differential gene expression analysis was performed and cross-validated with proteomics results to identify common genes/proteins between them. A functional enrichment pathway analysis was performed. Cross-validation analysis revealed five differentially expressed genes, namely FGL2, IGFBP5, NNMT, PLA2G2A, and TNC, in patients with AF compared with those with sinus rhythm (SR). These genes play crucial roles in various cardiovascular functions and may be part of the molecular signature of AF. Furthermore, functional enrichment analysis revealed several pathways related to the extracellular matrix, inflammation, and structural remodeling. This study highlighted five key genes that constitute promising candidates for further experimental exploration as biomarkers as well as therapeutic targets for AF.

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Remodeling in Persistent Atrial Fibrillation: Pathophysiology and Therapeutic Targets—A Systematic Review

Roka

Burright

2023

Physiologia

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Atrial fibrillation (AF) is characterized by disorganized rapid atrial electrical activity, which leads to impaired atrial function, adverse hemodynamic effects, and increased thromboembolic risk. The paroxysmal forms of AF can be effectively treated with current pharmacological and non-pharmacological modalities by targeting the arrhythmia triggers. Persistent AF, however, is more difficult to treat due to remodeling processes which may become major factors in the maintenance of the arrhythmia, rendering trigger-targeting treatment options less effective. We will systematically review the recent findings of the development and maintenance of persistent AF, including genetic, cellular, organ level, and systemic processes. As AF remains the most common sustained arrhythmia with the ongoing need to find effective treatment, we will also discuss potential treatment options targeting the remodeling processes.

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Circulating proteomic patterns in AF related left atrial remodeling indicate involvement of coagulation and complement cascade

Abstract: Background: Left atrial (LA) electro-anatomical remodeling and diameter increase in atrial

Cited by 3 publications

References 32 publications

Weighted gene co‑expression network analysis to identify key modules and hub genes associated with atrial fibrillation

Weighted gene co‑expression network analysis to identify key modules and hub genes associated with atrial fibrillation

Beyond the Rhythm: In Silico Identification of Key Genes and Therapeutic Targets in Atrial Fibrillation

Remodeling in Persistent Atrial Fibrillation: Pathophysiology and Therapeutic Targets—A Systematic Review

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