Causal relationship between immune cells and atrial fibrillation: A Mendelian randomization study.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia, with recent research indicating a correlation between immune system characteristics and the development of AF. However, it remains uncertain whether the immunological response is the primary underlying component or a secondary consequence of AF. Initially, we investigated the effect of immune cells on AF by performing forward Mendelian randomization (MR) analyses with immune cells as the exposure variable and their associated genetic variants as instrumental variables. Subsequently, we performed reverse MR analyses with AF as the exposure variable and immune cells as the outcome variable to exclude the interference of reverse causality, to distinguish between primary and secondary effects, and to further elucidate the causal relationship between the immune system and AF. We discovered that membrane proteins on specific immune cells, such as CD25 on memory B cells-which functions as a part of the interleukin-2 receptor-may be risk factors for AF development, with odds ratios of 1.0233 (95% confidence interval: 1.0012-1.0458, P = .0383). In addition, certain immune cell counts, such as the CD4 regulatory T cell Absolute Count, play a protective factor in the development of AF (odds ratio: 0.9513, 95% confidence interval: 0.9165-0.9874; P = .0086). More detailed results are elaborated in the main text. Our MR study has yielded evidence that substantiates a genetically inferred causal association between the immune system and AF. Identifying the risk factors associated with AF is vital to facilitate the development of innovative pharmaceutical treatments.

Recruited macrophages elicit atrial fibrillation.

Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune and stromal cells contribute to atrial fibrillation. Single-cell transcriptomes from human atria documented inflammatory monocyte and SPP1+ macrophage expansion in atrial fibrillation. Combining hypertension, obesity, and mitral valve regurgitation (HOMER) in mice elicited enlarged, fibrosed, and fibrillation-prone atria. Single-cell transcriptomes from HOMER mouse atria recapitulated cell composition and transcriptome changes observed in patients. Inhibiting monocyte migration reduced arrhythmia in Ccr2-∕- HOMER mice. Cell-cell interaction analysis identified SPP1 as a pleiotropic signal that promotes atrial fibrillation through cross-talk with local immune and stromal cells. Deleting Spp1 reduced atrial fibrillation in HOMER mice. These results identify SPP1+ macrophages as targets for immunotherapy in atrial fibrillation.

Identification of Potential Key Biomarkers of Atrial Fibrillation and Their Correlation with Immune Infiltration in Atrial Tissue.

Objective: To identify potential key biomarkers and characterize immune infiltration in atrial tissue of patients with atrial fibrillation (AF) through bioinformatics analysis. Methods: Differentially expressed genes (DEGs) were identified by the LIMMA package in Bioconductor, and functional and pathway enrichment analyses were undertaken using GO and KEGG. The LASSO logistic regression and BORUTA algorithm were employed to screen for potential novel key markers of AF from all DEGs. Gene set variation analysis was also performed. Single-sample gene set enrichment analysis was employed to quantify the infiltration levels for each immune cell type, and the correlation between hub genes and infiltrating immune cells was analyzed. Results: A total of 52 DEGs were identified, including of 26 downregulated DEGs and 26 upregulated DEGs. DEGs were primarily enriched in the Major Histocompatibility Complex class II protein complex, glucose homeostasis, protein tetramerization, regulation of synapse organization, cytokine activity, heart morphogenesis, and blood circulation. Three downregulated genes and three upregulated genes were screened by LASSO logistic regression and the BORUTA algorithm. Finally, immune infiltration analysis indicated that the atrial tissue of AF patients contained significant infiltration of APC_co_inhibition, Mast_cell, neutrophils, pDCs, T_cell_costimulation, and Th1_cells compared with paired sinus rhythm (SR) atrial tissue, and the three downregulated genes were negatively correlated with the six kinds of immune cells mentioned above. Conclusion: The hub genes identified in this study and the differences in immune infiltration of atrial tissue observed between AF and SR tissue might help to characterize the occurrence and progression of AF.

The systemic-immune-inflammation index predicts the recurrence of atrial fibrillation after cryomaze concomitant with mitral valve surgery.

BACKGROUND AND AIMS: Inflammation plays a key role in the initiation and progression of atrial fibrillation (AF). The systemic inflammation indexes are easily evaluated and predict AF development. However, it's role in prediction of recurrence of AF is unknown. We aim to explore the association between the systemic inflammation indexes and recurrence of AF in patients underwent cryoablation (CryoMaze) concomitant with mitral valve surgery. METHODS: We examined systemic inflammation indexes during perioperative period in 122 patients between 2015 and 2018. Systemic inflammation indexes were developed by systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocytes to monocytes ratio. Univariate and multivariate analyses were performed to examine the association of each markers with recurrence of AF. RESULTS: Of the 122 patients included in this study, 22 patients (18%) experienced AF recurrence after CryoMaze concomitant with mitral valve surgery. There is no significant difference between each systemic inflammation indexes before surgery and recurrence of AF. In univariate analysis, MLR after surgery 3 days, PLR, MPLR, NLR, SII after surgery 7 days were able to predict recurrence of AF. In multivariate analyses, SII ≥ 1696 independently predicted recurrence (OR, 3.719; 95% CI, 1.417-9.760). Interestingly, baseline SII showed no significant in prediction of recurrence. It was sharply elevated after surgery and dropped slowly. In patients of recurrence, SII after 7 days of surgery increased again. CONCLUSIONS: The raised SII again was associated with an increased risk of the postoperative recurrence of AF and independently predicted the late recurrence of AF after CryoMaze concomitant with mitral valve surgery.

Predictive value of lymphocyte-to-monocyte ratio in critically Ill patients with atrial fibrillation: A propensity score matching analysis.

BACKGROUND: Inflammation plays a key role in the initiation and progression of atrial fibrillation (AF). Lymphocyte-to-monocyte ratio (LMR) has been proved to be a reliable predictor of many inflammation-associated diseases, but little data are available on the relationship between LMR and AF. We aimed to evaluate the predictive value of LMR in predicting all-cause mortality among AF patients. METHODS: Data of patients diagnosed with AF were retrieved from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. X-tile analysis was used to calculate the optimal cutoff value for LMR. The Cox regression model was used to assess the association of LMR and 28-day, 90-day, and 1-year mortality. Additionally, a propensity score matching (PSM) method was performed to minimize the impact of potential confounders. RESULTS: A total of 3567 patients hospitalized with AF were enrolled in this study. The X-tile software indicated that the optimal cutoff value of LMR was 2.67. A total of 1127 pairs were generated, and all the covariates were well balanced after PSM. The Cox proportional-hazards model showed that patients with the low LMR (≤2.67) had a higher 1-year all-cause mortality than those with the high LMR (>2.67) in the study cohort before PSM (HR = 1.640, 95% CI: 1.437-1.872, p < 0.001) and after PSM (HR = 1.279, 95% CI: 1.094-1.495, p = 0.002). The multivariable Cox regression analysis for 28-day and 90-day mortality yielded similar results. CONCLUSIONS: The lower LMR (≤2.67) was associated with a higher risk of 28-day, 90-day, and 1-year all-cause mortality, which might serve as an independent predictor in AF patients.

Immunothrombosis and new-onset atrial fibrillation in the general population: the Rotterdam Study.

BACKGROUND: Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia. The etiology underlying AF is still largely unknown. At the intersection of the innate immune system and hemostasis, immunothrombosis may be a possible cause of atrial remodeling, and therefore be an underlying cause of AF. METHODS: From 1990 to 2014, we followed participants aged 55 and over, free from AF at inclusion. Immunothrombosis factors fibrinogen, von Willebrand factor, ADAMTS13, and neutrophil extracellular traps (NETs) levels were measured at baseline. Participants were followed until either onset of AF, loss-to-follow-up, or reaching the end-date of 01-01-2014. Cox proportional hazard modelling was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for cardiovascular risk factors. RESULTS: We followed 6174 participants (mean age 69.1 years, 57% women) for a median follow-up time of 12.8 years. 364 men (13.7%, incidence rate 13.0/1000 person-years) and 365 women (10.4%, incidence rate 8.9/1000 person-years) developed AF. We found no significant association between markers of immunothrombosis and new-onset AF after adjusting for cardiovascular risk factors [HR 1.00 (95% CI 0.93-1.08) for fibrinogen, 1.04 (0.97-1.12) for von Willebrand factor, 1.00 (1.00-1.01) for ADAMTS13, and 1.01 (0.94-1.09) for NETs]. In addition, we found no differences in associations between men and women. CONCLUSION: We found no associations between markers of immunothrombosis and new-onset AF in the general population. Inflammation and immunothrombosis may be associated with AF through other cardiovascular risk factors or predisposing conditions of AF. Our findings challenge the added value of biomarkers in AF risk prediction.

Ferroportin-mediated ferroptosis involved in new-onset atrial fibrillation with LPS-induced endotoxemia.

Sepsis is a known risk factor for new-onset atrial fibrillation (AF), and previous studies have demonstrated that ferroptosis participates in sepsis-induced organ injury development. Nevertheless, the role of ferroptosis in new-onset AF with sepsis remains largely unknown. This study aims to investigate the underlying mechanisms linking ferroptosis and AF caused by sepsis. LPS-induced endotoxemia is often used to model the acute inflammatory response associated with sepsis. Herein, we reported that ferroptosis was significantly activated in LPS-induced endotoxemia rat model. We also observed that ferroportin (Fpn), the only identified mammalian non-heme iron exporter, was downregulated in the atrium of endotoxemia model. Vulnerability to AF was also significantly increased in a endotoxemia rat model. Additionally, Fpn knockdown by shFpn further increased intracellular iron concentration and oxidative stress and exaggerated the AF vulnerability, which was alleviated by ferroptosis inhibition. Mechanistically, silencing Fpn worsened the alterations in calcium handling proteins expression in a endotoxemia rat model. These findings suggest that Fpn-mediated ferroptosis is involved in the new-onset AF with LPS-induced endotoxemia via worsening the calcium handling proteins dysregulation and provides a novel and promising strategy for preventing AF development in sepsis.

Elevated Peripheral T Helper Cells Are Associated With Atrial Fibrillation in Patients With Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have a significantly high risk of atrial fibrillation (AF). This study aimed to compare the absolute and relative changes in peripheral T cells in patients with RA who were also affected with and without AF. To help make an early diagnosis and prevent the initiation and progression of AF, the changes in the lymphocyte subsets were assessed in RA patients with and without AF. A propensity score matching (PSM) system (1:3) was used to perform a matched case-control study with 40 RA-AF cases and 120 RA controls. Changes in the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-citrullinated peptide antibody (ACPA), and rheumatoid factor (RF) were examined. The percentage and absolute number of T, B, natural killer (NK), T helper (Th)1, Th2, Th17, and T-regulatory (Treg) cells in the peripheral blood of patients with and without RA-AF were determined using flow cytometry. Univariate and multivariate analyses were performed to determine the association between peripheral lymphocytes and RA-AF. Demographic data, ESR, CRP, ACPA, and the percentage, as well as the absolute value of B, NK, Th2, and Treg cells, showed no significant differences between the propensity score-matched groups of RA and RA-AF. Meanwhile, the absolute number and percentage of Th1 cells, the absolute number of Th17 cells, the ratio of Th1/Treg, Th17/Treg, and RF were significantly higher in patients with RA-AF than those in the control groups (P < 0.05). Univariate and multivariate logistic regression analyses also revealed that the percentage of Th1 cells, the absolute number of Th17 cells, and the ratio of Th1/Treg were associated with a significantly higher risk of AF. This PSM study demonstrated that the incidence of AF was higher in RA patients with Th cell immunological derangements.

The impact of CD4+CD28null T lymphocytes on atrial fibrillation: a potential pathophysiological pathway.

INTRODUCTION: Atrial fibrillation (AF) represents the most common cardiac arrhythmia in daily clinical practice and substantially impacts affected patients by elevation of both morbidity and mortality. Previous investigations proved that inflammatory processes are closely linked to this multifactorial pathogenesis-especially autoreactive CD4+CD28null T cells received in-depth attention. PURPOSE: Consequently, a potential pathophysiological pathway of the impact of CD4+CD28null T lymphocytes on the development and progression AF can be outlined. CONCLUSION: Considering the available data in the literature, it needs to be assumed that CD4+CD28null T lymphocytes are mainly involved in the development of AF and disease progression. Of utmost importance, it can be considered as the result of a T-cell-mediated auto-immune reaction among myocardial tissue. However, mechanisms which recruit CD4+CD28null cells in cardiac tissue remain unclear and need further investigation.

Exercising immune cells: The immunomodulatory role of exercise on atrial fibrillation.

Exercise training is generally beneficial for cardiovascular health, improving stroke volume, cardiac output, and aerobic capacity. Despite these benefits, some evidence indicates that endurance training may increase the risk of atrial fibrillation (AF), particularly in highly trained individuals. Among multiple mechanisms, autonomic tone changes and atrial remodeling have been proposed as main contributors for exercise-induced AF. However, the contribution of local and systemic immunity is poorly understood in the development of atrial arrhythmogenic substrates. Here we aim to update the field of immunomodulation in the context of exercise and AF by compiling and reconciling the most recent evidence from preclinical and human studies and rationalize the applicability of "lone" AF terminology in athletes.

Neutrophil-to-lymphocyte ratio associated with an increased risk of mortality in patients with critical limb ischemia.

PURPOSE: Association of the neutrophil-to-lymphocyte ratio (NLR) with mortality has not been comprehensively explored in critical limb ischemia (CLI) patients. We investigated the association between the NLR and clinical outcomes in CLI. MATERIALS AND METHODS: We retrospectively enrolled consecutive CLI patients between 1/1/2013 and 12/31/2018. Receiver operating characteristic curve analysis determined NLR cutoffs for 1-year in-hospital, all-cause and cardiac-related mortality; major adverse cardiovascular events (MACEs); and major adverse limb events (MALEs). RESULTS: Among 195 patients (age, 74.0 years, SD: 11.5; 51.8% male; body mass index, 23.4 kg/m2, SD: 4.2), 14.4% exhibited acute limb ischemia. After 1 year, patients with NLR>8 had higher in-hospital mortality (21.1% vs. 3.6%, P<0.001), all-cause mortality (54.4% vs. 13.8%, P<0.001), cardiac-related mortality (28.1% vs. 6.5%, P<0.001), MACE (29.8% vs. 13.0%, P = 0.008), and MALE (28.1% vs. 13.0%, P = 0.021) rates than those with NLR<8. In multivariate logistic regression, NLR≥8 was significantly associated with all-cause (P<0.001) and cardiac-related (adjusted HR: 5.286, 95% CI: 2.075-13.47, P<0.001) mortality, and NLR≥6 was significantly associated with MALEs (adjusted HR: 2.804, 95% CI: 1.292-6.088, P = 0.009). Each increase in the NLR was associated with increases in all-cause (adjusted HR: 1.028, 95% CI: 1.008-1.049, P = 0.007) and cardiac-related (adjusted HR:1.027, 95% CI: 0.998-1.057, P = 0.073) mortality but not in-hospital mortality or MACEs. CONCLUSION: CLI patients with high NLRs had significantly higher risks of 1-year all-cause and cardiac-related mortality and MALEs. The NLR can be used for prognostic prediction in these patients.

Comprehensive analysis of autophagy-related genes and patterns of immune cell infiltration in valvular atrial fibrillation.

BACKGROUND: The development of atrial fibrillation (AF) following valvular heart disease (VHD) remains a common disease and is associated with substantial adverse complications. However, valid molecular diagnostic and therapeutic tools for post-VHD AF have not been fully established. This study was conducted to discover the molecular mechanisms and immune microenvironment underlying AF following VHD. METHODS: Gene expression profiles of the GSE41177 dataset were assessed to construct a protein-protein interaction network, and then, autophagy-related hub genes were identified. In addition, to determine the functions of immune cell infiltration in valvular AF, we used the CIBERSORT algorithm to estimate the composition of 22 immune cell types in valvular heart disease. Finally, correlation analysis was carried out to identify the relationship between differentially expressed autophagy-related genes (DEARGs) and significant immune cell subpopulations to reveal potential regulatory pathways. RESULTS: A total of 153 DEARGs were identified in AF-VHD patients compared with controlled donors. Moreover, we screened the top ten hub nodes with the highest degrees through a network analysis. The ten hub nodes were considered hub genes related to AF genesis and progression. Then, we revealed six significant immune cell subpopulations through the CIBERSORT algorithm. Finally, correlation analysis was performed, and six DEARGs (BECN1, GAPDH, ATG7, MAPK3, BCL2L1, and MYC) and three immune cell subpopulations (T cells CD4 memory resting, T cells follicular helper, and neutrophils) were identified as the most significant potential regulators. CONCLUSION: The DEARGs and immune cells identified in our study may be critical in AF development following VHD and provide potential predictive markers and therapeutic targets for determining a treatment strategy for AF patients.

Immuno-Electrophysiological Mechanisms of Functional Electrical Connections Between Recipient and Donor Heart in Patients With Orthotopic Heart Transplantation Presenting With Atrial Arrhythmias.

[Figure: see text].

Neutrophil degranulation interconnects over-represented biological processes in atrial fibrillation.

Despite our expanding knowledge about the mechanism underlying atrial fibrillation (AF), the interplay between the biological events underlying AF remains incompletely understood. This study aimed to identify the functionally enriched gene-sets in AF and capture their interconnection via pivotal factors, that may drive or be driven by AF. Global abundance of the proteins in the left atrium of AF patients compared to control patients (n = 3/group), and the functionally enriched biological processes in AF were determined by mass-spectrometry and gene set enrichment analysis, respectively. The data were validated in an independent cohort (n = 19-20/group). In AF, the gene-sets of innate immune system, metabolic process, cellular component disassembly and ion homeostasis were up-regulated, while the gene-set of ciliogenesis was down-regulated. The innate immune system was over-represented by neutrophil degranulation, the components of which were extensively shared by other gene-sets altered in AF. In the independent cohort, an activated form of neutrophils was more present in the left atrium of AF patients with the increased gene expression of neutrophil granules. MYH10, required for ciliogenesis, was decreased in the atrial fibroblasts of AF patients. We report the increased neutrophil degranulation appears to play a pivotal role, and affects multiple biological processes altered in AF.

Morpho-functional changes of cardiac telocytes in isolated atrial amyloidosis in patients with atrial fibrillation.

Telocytes are interstitial cells with long, thin processes by which they contact each other and form a network in the interstitium. Myocardial remodeling of adult patients with different forms of atrial fibrillation (AF) occurs with an increase in fibrosis, age-related isolated atrial amyloidosis (IAA), cardiomyocyte hypertrophy and myolysis. This study aimed to determine the ultrastructural and immunohistochemical features of cardiac telocytes in patients with AF and AF + IAA. IAA associated with accumulation of atrial natriuretic factor was detected in 4.3-25% biopsies of left (LAA) and 21.7-41.7% of right (RAA) atrial appendage myocardium. Telocytes were identified at ultrastructural level more often in AF + IAA, than in AF group and correlated with AF duration and mitral valve regurgitation. Telocytes had ultrastructural signs of synthetic, proliferative, and phagocytic activity. Telocytes corresponded to CD117+, vimentin+, CD34+, CD44+, CD68+, CD16+, S100-, CD105- immunophenotype. No significant differences in telocytes morphology and immunophenotype were found in patients with various forms of AF. CD68-positive cells were detected more often in AF + IAA than AF group. We assume that in aged AF + IAA patients remodeling of atrial myocardium provoked transformation of telocytes into "transitional forms" combining the morphological and immunohistochemical features with signs of fibroblast-, histiocyte- and endotheliocyte-like cells.

Comprehensive Analysis of Differential Immunocyte Infiltration and Potential ceRNA Networks Involved in the Development of Atrial Fibrillation.

This study is aimed at identifying potential molecular mechanisms and candidate biomarkers in the left atrial regions for the diagnosis and treatment of valvular atrial fibrillation (VAF). Multibioinformatics methods, including linear models for microarray analysis (LIMMA), an SVA algorithm, CIBERSORT immune infiltration, and DNA methylation analysis, were employed. In addition, the protein-protein interaction (PPI) network, Gene Ontology (GO), and molecular pathways of differentially expressed genes (DEGs) or differential methylation regions were constructed. In all, compared with the normal rhythm group, 243 different mRNAs (29 downregulated and 214 upregulated) and 26 different lncRNAs (3 downregulated and 23 upregulated) were detected in the left atrium (LA) of atrial fibrillation (AF) patients, and the neutrophil and CD8+ T cell were infiltrated. Additionally, 199 different methylation sites (107 downregulated and 92 upregulated) were also identified based on DNA methylation analysis. After integration, ELOVL2, CCR2, and WEE1 were detected for differentially methylated and differentially transcribed genes. Among them, WEE1 was also a core gene identified by the competing endogenous RNA (ceRNA) network that included WEE1-KRBOX1-AS1-hsa-miR-17-5p, in VAF left atrial tissue. We combined the DNA methylation and transcriptional expression differential analysis and found that WEE1 (cg13365543) may well be a candidate gene regulated by DNA methylation modification. Moreover, KRBOX1-AS1 and WEE1 can compete endogenously and may mediate myocardial tissue infiltration into CD8+ T cells and participate in the AF process.

CD8+CD28null T Lymphocytes are Associated with the Development of Atrial Fibrillation after Elective Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is assumed as a complex and multifactorial interaction of different pathogenic factors. Data suggests an inflammatory process as the main trigger of this specific type of atrial fibrillation. CD8+ T lymphocytes that lack the surface protein CD28 were found to be crucially involved in chronic inflammatory processes within the cardiovascular system. Of utmost interest, these so-called CD8+CD28null T cells are known to present with autoaggressive behavior and deleterious cytotoxic effects on human tissue. METHODS: A total of 129 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were enrolled. Fluorescence-activated cell sorting was performed to investigate lymphocyte subsets. Patients were stratified in two subgroups according to patients developing POAF (n = 60) and individuals free of POAF (n = 69). RESULTS: Comparing patients developing POAF to individuals free of POAF, the fraction of CD8+ lymphocytes was significantly higher in individuals developing POAF (30.5% [POAF] vs. 25.7% [no-POAF]; p = 0.021). Interestingly, also the fraction of CD8+CD28null T lymphocytes was significantly higher in the POAF subgroup (66.7% [POAF] vs. 61.6% [non-POAF]; p = 0.043). Multivariate logistic regression proved that the fraction of CD8+CD28null cells is a strong and independent prognosticator for the development of POAF with an adjusted odds ratio per 1 standard deviation of 3.21 (95% confidence interval 1.01-10.18; p = 0.048). CONCLUSION: We found that cytotoxic CD8+CD28null T lymphocytes proved to be a strong and independent predictor for the development of POAF after elective cardiac surgery. Our results potentially indicate an autoimmune impact of this preexisting, highly cytotoxic T cell subset in the pathogenesis of POAF.

The first case of COVID-19 treated with the complement C3 inhibitor AMY-101.

Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology. Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways. While a "cytokine storm" involving IL-6 and other cytokines has been documented, complement C3 activation has been implicated as an initial effector mechanism that exacerbates lung injury in preclinical models of SARS-CoV infection. C3-targeted intervention may provide broader therapeutic control of complement-mediated inflammatory damage in COVID-19 patients. Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101.

IL-6-miR-210 Suppresses Regulatory T Cell Function and Promotes Atrial Fibrosis by Targeting Foxp3.

The aim of this study was to explore the role of IL-6-miR-210 in the regulation of Tregs function and atrial fibrosis in atrial fibrillation (AF). The levels of interleukin (IL)-6 and IL-10 in AF patients were detected by using ELISA. Proportions of Treg cells were detected by fluorescence activated cell sorting analysis in AF patients. The expression of Foxp3, α-SMA, collagen I and collagen III were determined by western blot. The atrial mechanocytes were authenticated by vimentin immunostaining. The expression of miR-210 was performed by quantitative real-time polymerase chain reaction (qRT-PCR). TargetScan was used to predict potential targets of miR-210. The cardiomyocyte transverse sections in AF model group were observed by H&E staining. The myocardial filaments were observed by masson staining. The level of IL-6 was highly increased while the level of IL-10 (Tregs) was significantly decreased in AF patients as compared to normal control subjects, and IL-6 suppressed Tregs function and promoted the expression of α-SMA, collagen I and collagen III. Furthermore, miR-210 regulated Tregs function by targeting Foxp3, and IL-6 promoted expression of miR-210 via regulating hypoxia inducible factor-1α (HIF-1α). IL-6-miR-210 suppresses regulatory T cell function and promotes atrial fibrosis by targeting Foxp3.