Enhanced monocyte migratory activity in the pathogenesis of structural remodeling in atrial fibrillation

Miyosawa, Katsutoshi; Iwata, Hiroshi; Minami-Takano, Asuka; Hayashi, Hidemori; Tabuchi, Haruna; Sekita, Gaku; Kadoguchi, Tomoyasu; Ishii, Kai; Nozaki, Yui; Funamizu, Takehiro; Chikata, Yuichi; Matsushita, Satoshi; Amano, Atsushi; Sumiyoshi, Masataka; Nakazato, Yuji; Daida, Hiroyuki; Minamino, Tohru

doi:10.1371/journal.pone.0240540

Cited by 16 publications

(20 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that macrophages play an important role in arrhythmogenesis since they can produce a number of cytokines which have been linked to cardiac remodeling. However, only recently a few studies have been published that clearly demonstrate specific macrophage-dependent mechanisms regulating physiologic conduction ( Hulsmans et al, 2017 ; Sugita et al, 2021 ; Simon-Chica et al, 2022 ) as well as electrical, structural, or autonomic remodeling leading to arrhythmias ( Monnerat et al, 2016 ; Sun et al, 2016 ; Yin et al, 2016 ; Fei et al, 2019 ; Hu et al, 2019 ; Liu et al, 2019 ; Lubos et al, 2020 ; Lyu et al, 2020 ; Miyosawa et al, 2020 ; Zhang et al, 2020 ; Hiram et al, 2021 ; Zhang et al, 2021 ) ( Figure 2 ).…”

Section: Cardiac Macrophages Mediate Arrhythmogenesis By Promoting Ca...mentioning

confidence: 99%

“…Cardiac inflammatory responses e.g., in the context of myocardial infarction (MI) or heart failure (HF), are thought to crucially contribute to the proarrhythmic remodeling resulting in the development of vulnerable substrates in the heart ( Engelmann and Svendsen, 2005 ; Francis Stuart et al, 2016 ). Recently, studies have revealed the various roles played by immune cells, especially macrophages, in the maintenance of cardiac homeostasis ( Hulsmans et al, 2017 ; Sugita et al, 2021 ; Simon-Chica et al, 2022 ) and—if disrupted—the development of cardiac arrhythmias ( Monnerat et al, 2016 ; Sun et al, 2016 ; Yin et al, 2016 ; Fei et al, 2019 ; Hu et al, 2019 ; Liu et al, 2019 ; Lubos et al, 2020 ; Lyu et al, 2020 ; Miyosawa et al, 2020 ; Zhang et al, 2020 ; Hiram et al, 2021 ; Zhang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Pro-inflammatory macrophages release cytokines and chemokines and have been demonstrated to be involved in electrical ( Monnerat et al, 2016 ; Sun et al, 2016 ; Fei et al, 2019 ; Liu et al, 2019 ; Zhang et al, 2020 ) as well as autonomic remodeling of the heart ( Yin et al, 2016 ; Hu et al, 2019 ; Lyu et al, 2020 ; Zhang et al, 2021 ). Noncanonical reparative (or alternatively-activated) macrophages release anti-inflammatory cytokines, participate in post-inflammatory tissue repair, and contribute to cardiac structural remodeling by promoting cardiac fibrosis ( Wynn and Barron, 2010 ; Dobaczewski et al, 2011 ; Mills, 2012 ; Liao et al, 2018 ; Miyosawa et al, 2020 ; Watson et al, 2020 ; Hiram et al, 2021 ; Revelo et al, 2021 ). Furthermore, it has been shown that cardiac resident macrophages are functionally connected to cardiomyocytes by gap junctions ( Simon-Chica et al, 2022 ), thereby facilitating the physiologic electrical conduction in the atrioventricular (AV) node ( Hulsmans et al, 2017 ) or preserving electrical conduction in the context of disease ( Sugita et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cardiac Macrophages and Their Effects on Arrhythmogenesis

et al. 2022

View full text Add to dashboard Cite

Cardiac electrophysiology is a complex system established by a plethora of inward and outward ion currents in cardiomyocytes generating and conducting electrical signals in the heart. However, not only cardiomyocytes but also other cell types can modulate the heart rhythm. Recently, cardiac macrophages were demonstrated as important players in both electrophysiology and arrhythmogenesis. Cardiac macrophages are a heterogeneous group of immune cells including resident macrophages derived from embryonic and fetal precursors and recruited macrophages derived from circulating monocytes from the bone marrow. Recent studies suggest antiarrhythmic as well as proarrhythmic effects of cardiac macrophages. The proposed mechanisms of how cardiac macrophages affect electrophysiology vary and include both direct and indirect interactions with other cardiac cells. In this review, we provide an overview of the different subsets of macrophages in the heart and their possible interactions with cardiomyocytes under both physiologic conditions and heart disease. Furthermore, we elucidate similarities and differences between human, murine and porcine cardiac macrophages, thus providing detailed information for researchers investigating cardiac macrophages in important animal species for electrophysiologic research. Finally, we discuss the pros and cons of mice and pigs to investigate the role of cardiac macrophages in arrhythmogenesis from a translational perspective.

show abstract

Section: Cardiac Macrophages Mediate Arrhythmogenesis By Promoting Ca...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cardiac Macrophages and Their Effects on Arrhythmogenesis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Through bioinformatics analysis, Gang Fan et al found that the expression of CCR2 was elevated in AF patients [ 43 ]. Miyosawa et al reported that the protein level of CCR2 was higher in isolated monocytes of AF patients whose left atrial diameter was larger [ 44 ]. Taken together, these reports are in agreement with our current demonstration that CCR2 , as a hub gene, was overexpressed in both NAFLD and AF datasets.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes and key pathways underlying the pathophysiological association between nonalcoholic fatty liver disease and atrial fibrillation

Chu

et al. 2022

BMC Med Genomics

View full text Add to dashboard Cite

Background Atrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias. The latest studies have revealed a tight correlation between nonalcoholic fatty liver disease (NAFLD) and AF. However, the exact molecular mechanisms underlying the association between NAFLD and AF remain unclear. The current research aimed to expound the genes and signaling pathways that are related to the mechanisms underlying the association between these two diseases. Materials and methods NAFLD- and AF- related differentially expressed genes (DEGs) were identified via bioinformatic analysis of the Gene Expression Omnibus (GEO) datasets GSE63067 and GSE79768, respectively. Further enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), the construction of a protein–protein interaction (PPI) network, the identification of significant hub genes, and receiver operator characteristic curve analysis were conducted. The gene-disease interactions were analyzed using the Comparative Toxicogenomics Database. In addition, the hub genes were validated by quantitative Real-Time PCR (qRT-PCR) in NAFLD cell model. Results A total of 45 co-expressed differentially expressed genes (co-DEGs) were identified between the NAFLD/AF and healthy control individuals. GO and KEGG pathway analyses revealed that the co-DEGs were mostly enriched in neutrophil activation involved in the immune response and cytokine-cytokine receptor interactions. Moreover, eight hub genes were selected owing to their high degree of connectivity and upregulation in both the NAFLD and AF datasets. These genes included CCR2, PTPRC, CXCR2, MNDA, S100A9, NCF2, S100A12, and S100A8. Conclusions In summary, we conducted the gene differential expression analysis, functional enrichment analysis, and PPI analysis of DEGs in AF and NAFLD, which provides novel insights into the identification of potential biomarkers and valuable therapeutic leads for AF and NAFLD.

show abstract

“…For example, monocyte activation especially the enhanced migration ability plays a vital role in the pathogenesis of progression in atrial remodeling in AF patients. 8 The role of the competing endogenous RNA (ceRNA) network has attracted much attention in recent years. 9 As a novel type molecule with special biological functions, circRNAs can be used as microRNA (miRNA) sponge to competitively bind miRNAs, modulate alternative splicing, and regulate the expression of parental genes.…”

Section: Introductionmentioning

confidence: 99%

The Construction and Comprehensive Analysis of a ceRNA Immunoregulatory Network and Tissue-Infiltrating Immune Cells in Atrial Fibrillation

Liu¹,

Zhong²,

Li³

et al. 2021

IJGM

View full text Add to dashboard Cite

Background: At present, the mechanisms behind atrial fibrillation (AF) pathogenesis are still unclear. We construct a ceRNA immunoregulatory network to further understand the mechanism of AF. Methods: Four AF mRNA datasets from the Gene Expression Omnibus (GEO) database were integrated by SVA method. AF-related immune genes (AF-IRGs) were selected via combining ImmPort database with the genes in the module most associated with AF obtained by a weighted gene coexpression network analysis (WGCNA). Then, circRNA and miRNA expressions from the GEO database were extracted and mapped with related databases. Next, an immune-related circRNA-miRNA-mRNA ceRNA network was constructed and hub genes were filtered from a protein-protein interaction (PPI) network, and the differentially expressed (DE) hub genes in AF were further screened. Additionally, immune infiltration was investigated in AF by using CIBERSORT. Subsequently, the relationships between DE hub genes and AF-related infiltrating immune cells were performed by using Pearson correlation coefficients. Ulteriorly, the immune-cells-related ceRNA subnetwork in AF was built. Results: A total of 95 AF-IRGs were detected, and an immune-related ceRNA network in AF was constructed with 12 circRNAs, 7 miRNAs and 50 mRNAs. The immune infiltration analysis indicated that a higher level of neutrophils, as well as a lower level of T cells regulatory (Tregs) and NK cells activated in AF. Four DE hub genes (CXCL12, IL7R, TNFSF13B, CD8A) were associated with Tregs or NK cells activated immune cells (P < 0.05). Tregs or NK cells activated immune cells-related ceRNA subnetwork including 5 circRNAs (has_circ_0001190, has_circ_0006725, has_circ_0079284, has_circ_0005299, and has_circ_0002103), 4 miRNAs (has-miR-198, has-miR-623, has-miR-1246, and has-miR -339-3p) and 4 DE hub genes was eventually constructed in AF. Conclusion: Our results provide new insights into the molecular mechanisms governing AF progression from the perspective of immune-related ceRNA network.

show abstract

Enhanced monocyte migratory activity in the pathogenesis of structural remodeling in atrial fibrillation

Cited by 16 publications

References 38 publications

Cardiac Macrophages and Their Effects on Arrhythmogenesis

Cardiac Macrophages and Their Effects on Arrhythmogenesis

Identification of genes and key pathways underlying the pathophysiological association between nonalcoholic fatty liver disease and atrial fibrillation

The Construction and Comprehensive Analysis of a ceRNA Immunoregulatory Network and Tissue-Infiltrating Immune Cells in Atrial Fibrillation

Contact Info

Product

Resources

About