Epicardial Adipose Tissue In Patients Research Articles

Long noncoding RNA and messenger RNA profiling in epicardial adipose tissue of patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting

BackgroundPostoperative atrial fibrillation (POAF) constitutes a significant complication following coronary artery bypass graft surgery (CABG), potentially linked to epicardial adipose tissue (EAT). This investigation seeks to elucidate the association between POAF and EAT at the genetic level.MethodsEAT and clinical data from patients undergoing CABG were systematically acquired, adhering to established inclusion and exclusion criteria. Patients were categorized into POAF and Non-POAF groups based on the presence or absence of POAF. High-throughput sequencing data of EAT were subjected to differential expression analysis and gene function assessment. A random selection of long noncoding RNAs (lncRNAs) underwent quantitative real-time polymerase chain reaction (qRT-PCR) for validation of the high-throughput sequencing findings. Coexpression analysis was employed to elucidate the interactions between lncRNAs and messenger RNAs (mRNAs).ResultsRNA sequencing yielded a total of 69,685 transcripts (37,740 coding and 31,945 noncoding sequences), representing 16,920 genes. Within this dataset, 38 mRNAs and 12 lncRNAs exhibited differential expression between the POAF and Non-POAF groups (P < 0.05, fold change > 1.5). The qRT-PCR results for lncRNAs corroborated the sequencing findings (P < 0.01). Functional enrichment analysis of genes and the coexpression network indicated that these differentially expressed RNAs were primarily implicated in processes such as cell growth, differentiation, signal transduction, as well as influencing tissue fibrosis and ion transmembrane transport.ConclusionsThis study unveils a potential association between myocardial fibrosis and ion channels co-regulated by mRNAs and lncRNAs, closely linked to the emergence of new-onset POAF, after accounting for clinical risk factors. This discovery holds promise for further advances in clinical and fundamental research.

Mediterranean diet and epicardial adipose tissue in patients with atrial fibrillation treated with ablation: a substudy of the 'PREDIMAR' trial.

To analyse the relationship between Mediterranean diet (MedDiet) adherence and epicardial adipose tissue (EAT) in patients with atrial fibrillation (AF) and the association between EAT or MedDiet adherence at baseline with AF recurrence after ablation. We included 199 patients from the PREDIMAR trial (PREvención con DIeta Mediterránea de Arritmias Recurrentes), in a single centre in this substudy. All of them had a computed tomography with EAT measurement. Lifestyle and clinical characteristics were obtained at baseline. The traditional MedDiet pattern was defined according to the MedDiet Adherence Screener (MEDAS). Any documented AF > 30 s after ablation was considered a recurrence. Multivariable-adjusted linear and logistic regression models were run to assess the cross-sectional association of MedDiet with EAT, and of EAT with the AF type at baseline. Also, Cox regression models were used to prospectively assess the associations of MedDiet adherence and EAT with AF recurrences after ablation. Median EAT was 135 g (interquartile range: 112-177), and the mean MedDiet score was 7.75 ± 2 points. A higher MEDAS ≥ 7 that was associated with lower odds of an EAT ≥ 135 g [multivariable odds ratio (mOR) = 0.45; 95% CI = 0.22-0.91; P = 0.025] was significantly associated with persistent AF after adjusting for traditional risk factors (mOR: 2.22; 95% CI: 1.03-4.79; P = 0.042). No significant associations were observed between EAT ≥ 135 g and the risk of atrial tachyarrhythmia recurrences after ablation [multivariable-adjusted hazard ratio (mHR) = 1.18; 95% CI: 0.72-1.94; P = 0.512], or between MEDAS ≥ 7 and AF recurrence (mHR = 0.78; 95% CI: 0.47-1.31; P = 0.344). In patients with AF, higher adherence to MedDiet is associated with a significantly lower amount of EAT. Epicardial adipose tissue ≥ 135 g was significantly associated with persistent AF.

Expression profiles and functional analysis of tRNA-derived small RNAs in epicardial adipose tissue of patients with heart failure

Background Heart failure is considered an epidemic disease in the modern world. Since it presents as a multifactorial, systemic disease, a comprehensive understanding of the underlying mechanism is essential. Epicardial adipose tissue (EAT) is increasingly recognized to be metabolically active and is able to secrete myriad bioactive molecules, including exosomes carrying tRNA-derived small RNAs (tsRNAs). Mounting evidence has suggested that these specific tsRNAs dynamically impact fundamental cellular processes, but no studies have focused on the influence of tsRNA in EAT on cardiac dysfunction. Methods To investigate the regulatory mechanism of tsRNAs of EAT associated with HF, we collected EAT from HF (n = 5) patients and controls (n = 5) and used a combination of RNA sequencing, quantitative reverse transcription-polymerase chain reaction (qRT–PCR) and bioinformatics to screen the expression profiles of tsRNAs in HF. Results We ultimately identified an expression profile of 343 tsRNAs in EAT. Of those, a total of 24 tsRNAs were significantly differentially expressed between HF and controls: 17 were upregulated and 7 were downregulated (fold change >1.5, p < 0.05). Four tsRNAs (tiRNA-Pro-TGG-001, tRF-Met-CAT-002, tRF-Tyr-GTA-010 and tRF-Tyr-GTA-011) were randomly selected and validated by qRT–PCR. Bioinformatics analyses revealed a dense interaction of target genes between tRF-Tyr-GTA-010 and tRF-Tyr-GTA-011. Based on functional analysis, these two tRFs might play a protective role by regulating sphingolipid and adrenergic signaling pathways by targeting genes mainly contributing to calcium ion transport. Conclusions Our study profiled tsRNA expression in EAT with HF and identified a comprehensive dimension of potential target genes and tsRNA-mRNA interactions.

Epicardial adipose tissue in patients with systemic sclerosis

Abstract Aims Epicardial adipose tissue (EAT) has emerged as a mediator between systemic inflammatory disorders and cardiovascular disease, and may therefore play a role in the pathophysiology of cardiac involvement in systemic sclerosis (SSc). The aim of this study was to assess the correlation between EAT and left ventricular (LV) function, and to determine the prognostic value of EAT in patients with SSc. Methods and results Consecutive patients with SSc who underwent non-contrast thorax computed tomography and echocardiography were included. EAT mass was quantified using dedicated software. The study endpoint was all-cause mortality. A total of 230 SSc patients (age 53 ± 15 years, 14% male) were included. The median value of EAT mass was 67 g (interquartile range: 45–101 g). Patients with increased EAT mass (≥67 g) showed more impaired LV diastolic function as compared with patients with less EAT mass (&amp;lt;67 g), and even after adjusting for age and comorbidities, EAT mass was independently associated with LV diastolic function parameters. During a median follow-up of 8 years, 42 deaths occurred. Kaplan–Meier analysis showed that patients with increased EAT mass had higher all-cause mortality rate as compared with patients with less EAT mass (29% vs. 7%; P &amp;lt; 0.001). In the multivariable analysis, EAT was independently associated with all-cause mortality after adjusting for important covariates (HR: 1.006; 95% CI: 1.001–1.010). Conclusion In patients with SSc, EAT is independently associated with LV diastolic dysfunction and higher mortality rate.

Epicardial adipose tissue in patients with chronic obstructive pulmonary disease: systematic review with meta‑analysis and trial sequential analysis

BackgroundLimited data suggest that chronic obstructive pulmonary disease (COPD) patients have pathologic elevated epicardial adipose tissue (EAT), which is splanchnic fat tissue with anti-inflammatory properties and regulating free fatty acids functions. Therefore, there is a need for meta-analysis to explore the relationship between EAT and COPD.MethodsOnline databases were systematically searched for studies about EAT in COPD patients published up to October 5th, 2022. The EAT data of the COPD patient group and the control group were included. Trial sequential analysis (TSA) and meta-analysis were applied to assess the difference in EAT between patients with and without COPD. TSA software and Stata 12.0 were used in all statistical analyses.ResultsThe final analysis included 5 studies (n = 596 patients). COPD patients had significantly more EAT than control subjects (SMD: 0.0.802; 95% CI: 0.231, 1.372; P = 0.006; TSA-adjusted 95% CI 1.20, 1.80; P < 0.0001). And higher CRP levels in COPD patients than non-COPD patients, whereas triglycerides and LDL were not significantly different between patients with and without COPD.ConclusionEAT is abnormally elevated in COPD patients, which may be related to systemic inflammatory responses in COPD.PROSPERO numberCRD42021228273.

Associations of aortic stiffness and intra-aortic flow parameters with epicardial adipose tissue in patients with type-2 diabetes.

It has been shown that increased aortic stiffness is related to type-2 diabetes (T2D) which is considered as a risk factor for cardiovascular disease. Among other risk factors is epicardial adipose tissue (EAT) which is increased in T2D and is a relevant biomarker of metabolic severity and adverse outcome. To assess aortic flow parameters in T2D patients as compared to healthy individuals and to evaluate their associations with EAT accumulation as an index of cardiometabolic severity in T2D patients. Thirty-six T2D patients as well as 29 healthy controls matched by age and sex were included in this study. Participants had cardiac and aortic MRI exams at 1.5 T. Imaging sequences included cine SSFP for left ventricle (LV) function and EAT assessment and aortic cine and phase-contrast imaging for strain and flow parameters quantification. In this study, we found LV phenotype to be characterized by concentric remodeling with decreased stroke volume index despite global LV mass within a normal range. EAT was increased in T2D patients compared to controls (p<0.0001). Moreover, EAT, a biomarker of metabolic severity, was negatively correlated to ascending aortic (AA) distensibility (p=0.048) and positively to the normalized backward flow volume (p=0.001). These relationships remained significant after further adjustment for age, sex and central mean blood pressure. In a multivariate model, presence/absence of T2D and AA normalized backward flow (BF) to forward flow (FF) volumes ratio are both significant and independent correlates of EAT. In our study, aortic stiffness as depicted by an increased backward flow volume and decreased distensibility seems to be related to EAT volume in T2D patients. This observation should be confirmed in the future on a larger population while considering additional biomarkers specific to inflammation and using a longitudinal prospective study design.

Sex Differences in the Regional Analysis of Nonpulmonary Vein Foci and Epicardial Adipose Tissue in Patients With Atrial Fibrillation

The mechanism underlying the sex differences in atrial fibrillation (AF) recurrence following pulmonary vein (PV) isolation is not fully understood. We hypothesized that non-PV foci and epicardial adipose tissue (EAT) play a key role.Methods and Results: Data from 304 consecutive patients (75% males) who underwent contrast-enhanced computed tomography and catheter ablation of AF were reviewed. The EAT around the atrium was measured separately in 4 parts of the atrium. All patients underwent high-dose isoproterenol infusions to assess the non-PV foci. Significantly more non-PV foci and less EAT around the atrium were observed in female patients than in male patients. In males, those with non-PV foci on the left atrial (LA) anterior wall had significantly greater EAT for the same lesions than those without non-PV foci. During a median follow-up of 27 months, the predictors of AF recurrence after first catheter ablation were female sex, presence of non-PV foci, LA diameter, and septal EAT index. A sex-specific analysis revealed that LA diameter was a predictor only in males and that the presence of non-PV foci in the septal region was a strong predictor in males (hazard ratio [HR]: 2.24) and females (HR: 3.65). Sex-specific differences were observed in non-PV foci sites and local EAT and in regard to the predictors of AF recurrence.

Epicardial adipose tissue in patients with systemic sclerosis

Abstract Background Cardiac involvement is a major cause of death in patients with systemic sclerosis (SSc). Epicardial adipose tissue (EAT) has recently emerged as a mediator between systemic inflammatory disorders and cardiovascular disease, and may therefore play a role in the pathophysiology of cardiac involvement in SSc. Purpose To assess the correlation between EAT mass and left ventricular (LV) function, and to determine the prognostic value of EAT in patients with SSc. Methods Consecutive patients with SSc who underwent non-contrast thorax computed tomography and echocardiography were included. EAT mass was quantified using dedicated software (Figure A). The study endpoint was all-cause mortality. Results A total of 230 SSc patients [age 53±15 years, 14% male] were included. The median value of EAT mass was 67g (IQR: 45–101g). Patients with increased EAT mass (≥67g) showed specifically more impaired LV diastolic function as compared to patients with less EAT mass (&amp;lt;67g). After adjusting for age and comorbidities, EAT remained independently associated with LV diastolic function parameters including left atrial volume index (B=0.031, P=0.025), LV mass index (B=0.139, P=0.036), E/E$'$ (B=0.025, P&amp;lt;0.001) and E' (B=−0.012, P&amp;lt;0.001). During a median follow-up of 8 years 42 patients died, and by Kaplan-Meier analysis patients with increased EAT mass showed higher all-cause mortality rate as compared to patients with less EAT mass (log-rank p&amp;lt;0.001, Figure B). On multivariate analysis, EAT mass was independently associated with all-cause mortality (HR: 1.006; 95% CI: 1.001–1.010; p=0.010). Conclusion In patients with SSc, EAT mass is independently associated with LV diastolic dysfunction and higher mortality rate. Funding Acknowledgement Type of funding sources: None.

Identification of key genes and mechanisms of epicardial adipose tissue in patients with diabetes through bioinformatic analysis.

BackgroundIn recent years, peri-organ fat has emerged as a diagnostic and therapeutic target in metabolic diseases, including diabetes mellitus. Here, we performed a comprehensive analysis of epicardial adipose tissue (EAT) transcriptome expression differences between diabetic and non-diabetic participants and explored the possible mechanisms using various bioinformatic tools.MethodsRNA-seq datasets GSE108971 and GSE179455 for EAT between diabetic and non-diabetic patients were obtained from the public functional genomics database Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified using the R package DESeq2, then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed. Next, a PPI (protein–protein interaction) network was constructed, and hub genes were mined using STRING and Cytoscape. Additionally, CIBERSORT was used to analyze the immune cell infiltration, and key transcription factors were predicted based on ChEA3.ResultsBy comparing EAT samples between diabetic and non-diabetic patients, a total of 238 DEGs were identified, including 161 upregulated genes and 77 downregulated genes. A total of 10 genes (IL-1β, CD274, PDCD1, ITGAX, PRDM1, LAG3, TNFRSF18, CCL20, IL1RN, and SPP1) were selected as hub genes. GO and KEGG analysis showed that DEGs were mainly enriched in the inflammatory response and cytokine activity. Immune cell infiltration analysis indicated that macrophage M2 and T cells CD4 memory resting accounted for the largest proportion of these immune cells. CSRNP1, RELB, NFKB2, SNAI1, and FOSB were detected as potential transcription factors.ConclusionComprehensive bioinformatic analysis was used to compare the difference in EAT between diabetic and non-diabetic patients. Several hub genes, transcription factors, and immune cell infiltration were identified. Diabetic EAT is significantly different in the inflammatory response and cytokine activity. These findings may provide new targets for the diagnosis and treatment of diabetes, as well as reduce potential cardiovascular complications in diabetic patients through EAT modification.

Epicardial Adipose Tissue in Patients with Coronary Artery Disease: A Meta-Analysis.

Objective: The aim of this study is to assess the association between epicardial adipose tissue (EAT) and coronary artery disease (CAD) via meta−analysis. Methods: Specific searches of online databases from January 2000 to May 2022 were conducted. All observational studies evaluating the association between EAT and CAD in PubMed, Web of Science, and the Cochrane Library databases were screened. A meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta−Analyses guidelines (PRISMA). In total, 21 studies encompassing 4975 subjects met the inclusion criteria, including 2377 diagnosed and assigned as the CAD group, while the other 2598 were assigned as the non−CAD group. Subjects in the CAD group were further divided into the severe stenosis group (stenosis ≥ 50%, n = 846) and the mild/moderate stenosis group (stenosis < 50%, n = 577). Results: Both the volume and thickness of EAT in the CAD group were larger compared to the non−CAD group (p < 0.00001). In a subgroup analysis within the CAD group, the severe stenosis group had a larger volume and thickness with respect to EAT when compared to the mild/moderate group (p < 0.001). Conclusions: The enlargement of EAT presented in CAD patients with an association with CAD severity. Although limited by different CAD types and measuring methods for EAT, as well as a smaller sample size, our results suggest that EAT is a novel predictor and a potential therapeutic target for CAD.

Molecular mechanisms of the development of atrial fibrillation in patients with type 2 diabetes mellitus: prognostic role of biomarkers of fibrosis and inflammation

The objective was to determine the concentrations of biomarkers of fibrosis and inflammation in the blood, parameters characterizing heart remodeling in patients with atrial fibrillation (AF) in combination with type 2 diabetes mellitus (T2DM).Methods and materials. The study included 231 examined patients aged 35 to 65 years: patients with DM (n=99), of which 49 patients with AF, and the comparison group consisted of patients with AF without T2DM (n=54) and healthy examined patients (n=78).Results. It was found that the concentration of profibrogenic biomarkers circulating in the blood of patients with AF and T2DM is higher than in patients with AF without T2DM: galectin-3 (13.4 (9.1–16.9) and 6.8 (4.6–12.8) ng/ml, p&lt;0.001), TGF-beta1 (3032.5 (2468.5–4283.5) and 2339.7 (1813.3–3368.8) pg/ml, p=0.01), GDF-15 (2359.3 (1234.3–3465.1) and 1256.7 (889.9–2083.7) pg/ml, p&gt;&lt;0.001), PINP (3625.4 (2462.1–4463.7) and 2451.3 (1842.0–2941.0) pg/ml, p&gt;&lt;0.001) and PIIINP (92.8 (68.6–122.4) and 67.6 (47.9–93.3) ng/ml, p&gt;&lt;0.001). Concentrations of proinflammatory cytokines CRP (3.5 (2.2–4.4) and 2.7 (1.4–7.1) mg/l, p=0.01) and CT-1 (1032.1 (667.6–1495.3) and 549.1 (411.9–960.1) pg/ml, p&gt;&lt;0.001) in patients with AF and T2DM is higher than in patients with T2DM without AF. The levels of TNF-alpha, IL-6 in patients with AF and T2DM are comparable to the concentrations of these biomarkers of inflammation in patients with T2DM without AF. According to the results of echocardiography, it was revealed that the thickness of the epicardial adipose tissue in patients with AF and T2DM is greater than in patients with AF without T2DM and greater than in patients with T2DM without AF (7.1±0.4, 4.5±0.3 and 5.1±0.3, respectively, p&gt;&lt;0.001). A strong positive correlation between GDF-15 and HbA1c was established according to the correlation analysis (r=0.617, p&gt;&lt;0.0001) and regression analysis (β=0.586, p&gt;&lt;0.0001). According to binomial logistic regression, it was found that T2DM in the examined cohort increased the risk of AF by 2.2 times (OR=2.2, 95 %CI 1.41–3.31, p=0.00004). Conclusion. The obtained new data on the increase in the concentration of profibrogenic factors in patients with AF in combination with T2DM indicate an important role of the formation of myocardial fibrosis in the development of this arrhythmia in these patients. Keywords: biomarkers, fibrosis, inflammation, atrial fibrillation, diabetes mellitus&gt;˂0.001), TGF-beta1 (3032.5 (2468.5–4283.5) and 2339.7 (1813.3–3368.8) pg/ml, p=0.01), GDF-15 (2359.3 (1234.3–3465.1) and 1256.7 (889.9–2083.7) pg/ml, p˂0.001), PINP (3625.4 (2462.1–4463.7) and 2451.3 (1842.0–2941.0) pg/ml, p˂0.001) and PIIINP (92.8 (68.6–122.4) and 67.6 (47.9–93.3) ng/ml, p˂0.001). Concentrations of proinflammatory cytokines CRP (3.5 (2.2–4.4) and 2.7 (1.4–7.1) mg/l, p=0.01) and CT-1 (1032.1 (667.6–1495.3) and 549.1 (411.9–960.1) pg/ml, p˂0.001) in patients with AF and T2DM is higher than in patients with T2DM without AF. The levels of TNF-alpha, IL-6 in patients with AF and T2DM are comparable to the concentrations of these biomarkers of inflammation in patients with T2DM without AF. According to the results of echocardiography, it was revealed that the thickness of the epicardial adipose tissue in patients with AF and T2DM is greater than in patients with AF without T2DM and greater than in patients with T2DM without AF (7.1±0.4, 4.5±0.3 and 5.1±0.3, respectively, p˂0.001). A strong positive correlation between GDF-15 and HbA1c was established according to the correlation analysis (r=0.617, p˂0.0001) and regression analysis (β=0.586, p˂0.0001). According to binomial logistic regression, it was found that T2DM in the examined cohort increased the risk of AF by 2.2 times (OR=2.2, 95 %CI 1.41–3.31, p=0.00004).Conclusion. The obtained new data on the increase in the concentration of profibrogenic factors in patients with AF in combination with T2DM indicate an important role of the formation of myocardial fibrosis in the development of this arrhythmia in these patients.

ANGPTL4 Expression Is Increased in Epicardial Adipose Tissue of Patients with Coronary Artery Disease.

Epicardial adipose tissue (EAT) is known to affect atherosclerosis and coronary artery disease (CAD) pathogenesis, persistently releasing pro-inflammatory adipokines that affect the myocardium and coronary arteries. Angiopoietin-like 4 (ANGPTL4) is a protein secreted from adipose tissue and plays a critical role in the progression of atherosclerosis. Here, the expression of ANGPTL4 in EAT was investigated in CAD subjects. Thirty-four consecutive patients (13 patients with significant CAD; 21 patients without CAD) undergoing elective open-heart surgery were recruited. EAT and pericardial fluid were obtained at the time of surgery. mRNA expression and ANGPTL4 and IL-1β levels were evaluated by qRT-PCR and ELISA. The expression of ANGPTL4 (p = 0.0180) and IL-1β (p < 0.0001) in EAT significantly increased in the CAD group compared to that in the non-CAD group and positively correlated (p = 0.004). Multiple regression analysis indicated that CAD is a contributing factor for ANGPTL4 expression in EAT. IL-1β level in the pericardial fluid was significantly increased in patients with CAD (p = 0.020). Moreover, the expression of ANGPTL4 (p = 0.004) and IL-1β (p < 0.001) in EAT was significantly increased in non-obese patients with CAD. In summary, ANGPTL4 expression in EAT was increased in CAD patients.

Association Between Systemic Inflamatuary Index and Epicardial Adipose Tissue in Patients with Type 2 Diabetes Mellitus

Objective: Epicardial adipose tissue is the visceral fat located between the myocardium and the pericardium. Increases in epicardial adipose tissue are closely associated with the occurrence of cardiovascular diseases. The systemic immune inflammation index is a new parameter developed to determine the inflammatory status of patients. In our study, we aimed to evaluate the relationship between systemic immun inflammation index and epicardial adipose tissue in patients with diabetes mellitus. Method: 119 patients with T2DM and 50 volunteers were included to study. SII was obtained with formulatıon of neutrophil/lymphocyte x platelet. Epicardial fat tissue was obtained by transthoracic echocardiography. The relationship between systemic immune inflammation index and epicardial adipose tissue was evaluated in patients with Diabetes Mellitus Results: In our study, ıt was shown that epicardial adipose tissue was higher in diabetic patients. There was a significant correlation between Body surface area , duration of diabetes mellitus, HbA1c, systemic immune inflammation index, mean platelet volume , neutrophil lymphocyte ratio and epicardial adipose tissue. In linear regression analysis, it was observed that duration of diabetes mellitus (β =0.049 (0.011-0.087); P=0.011) and SII (β=0.013 (0.001-0.018) P=0.008) were independent predictors of EAT. Conclusions: In our study, it was shown that there is a significant relationship between epicardial adipose tissue and systemic immune inflammation index in diabetic patients. In patients with diabetes mellitus, systemic immune inflammation index may provide a useful estimate of epicardial adipose tissue, which has been shown to be associated with cardiovascular events.

The Quantity of Epicardial Adipose Tissue in Patients Having Ablation for Atrial Fibrillation With and Without Heart Failure

The distribution of epicardial adipose tissue (EAT) across the spectrum of heart failure (HF) has yet to be fully elucidated. The present study investigated the distribution of EAT in an HF spectrum and its association with clinical and echocardiographic parameters. A total of 326 patients who underwent contrast-enhanced computed tomography before transcatheter atrial fibrillation ablation with and without HF symptoms, and a wide range of left ventricular (LV) ejection fractions (LVEF) were included. EAT mass was quantified on contrast-enhanced computed tomography using dedicated software. A total of 36 patients had HF with reduced LVEF (HFrEF) (11.0%), 46 had HF with mid-range LVEF (HFmrEF) (14.1%), 53 had HFpEF (16.3%), and 191 did not have HF symptoms (58.6%) and were considered controls. Patients with HFpEF had the largest EAT mass, significantly higher than the control group (128 ± 36 g vs 95 ± 35 g, p <0.001), the HFmrEF group (101 ± 37 g, p <0.001), and the HFrEF group (103 ± 37 g, p=0.002). However, there were no differences in EAT mass between patients with HFrEF, HFmrEF, and controls. EAT was independently associated with E/e', LV mass index, and tricuspid regurgitation velocity. Male gender, body mass index, and C-reactive protein levels were independently associated with EAT. In conclusion, patients with HFpEF had more EAT than patients with HFmrEF, patients with HFpEF, and controls. EAT was associated with worse LV diastolic dysfunction, whereas C-reactive protein levels were independently associated with EAT, suggesting an active inflammatory component.

ABCA1 and ABCG1 DNA methylation in epicardial adipose tissue of patients with coronary artery disease

BackgroundRecent studies have focused on the potential role of epicardial adipose tissue (EAT) in the development of coronary artery disease (CAD). ABCA1 and ABCG1 transporters regulate cell cholesterol content and reverse cholesterol transport. We aimed to determine whether DNA methylation and mRNA levels of the ABCA1 and ABCG1 genes in EAT and subcutaneous adipose tissue (SAT) were associated with CAD.MethodsPaired EAT and SAT samples were collected from 82 patients undergoing elective cardiac surgery either for coronary artery bypass grafting (CAD group, N = 66) or valve surgery (NCAD group, N = 16). ABCA1 and ABCG1 mRNA levels in EAT and SAT samples were analyzed using real time polymerase chain reaction, ABCA1 protein levels in EAT samples were assessed by western blotting. ABCA1 and ABCG1 DNA methylation analysis was performed in 24 samples from the CAD group and 9 samples from the NCAD group via pyrosequencing.ResultsDNA methylation levels in the ABCA1 promoter and ABCG1 cg27243685 and cg06500161 CpG sites were higher in EAT samples from patients with CAD compared with NCAD (21.92% vs 10.81%, p = 0.003; 71.51% vs 68.42%, p = 0.024; 46.11% vs 37.79%, p = 0.016, respectively). In patients with CAD, ABCA1 and ABCG1 DNA methylation levels were higher in EAT than in SAT samples (p < 0.05). ABCA1 mRNA levels in EAT samples were reduced in the subgroup of patients with CAD and concomitant carotid artery disease or peripheral artery disease compared with the NCAD group (p = 0.024). ABCA1 protein levels in EAT samples tended to be lower in CAD patients than in the NCAD group (p = 0.053). DNA methylation levels at the ABCG1 cg27243685 site positively correlated with plasma triglyceride concentration (r = 0.510, p = 0.008), body mass index (r = 0.556, p = 0.013) and waist-to-hip ratio (r = 0.504, p = 0.012) in SAT samples.ConclusionCAD is associated with ABCA1 and ABCG1 DNA hypermethylation in EAT. CAD with concomitant carotid artery disease or peripheral artery disease is accompanied by decreased ABCA1 gene expression in EAT. DNA methylation levels at the ABCG1 cg27243685 locus in SAT are associated with hypertriglyceridemia and obesity.

Detection of fibrotic remodeling of epicardial adipose tissue in patients with atrial fibrillation: Imaging approach based on histological observation.

BackgroundFibrotic remodeling of epicardial adipose tissue (EAT) is crucial for proinflammatory atrial myocardial fibrosis, which leads to atrial fibrillation (AF).ObjectivesWe tested the hypothesis that the ratio of central to marginal adipocyte diameter in EAT represents its fibrotic remodeling. Based on a similar concept, we also tested whether the percent (%) change in EAT fat attenuation determined using computed tomographic (CT) images can detect this remodeling.MethodsLeft atrial appendages were obtained from 76 consecutive AF patients during cardiovascular surgery. EAT in the central area (central EAT: C-EAT) and that adjacent to the atrial myocardium (Marginal EAT: M-EAT) were evaluated histologically. CT images for all of the 76 patients were also analyzed.ResultsThe adipocyte diameter was smaller, fibrotic remodeling of EAT (EAT fibrosis) was more severe, and infiltration of macrophages and myofibroblasts was more extensive in M-EAT than in C-EAT. EAT fibrosis was positively correlated with adipocyte diameter in C-EAT and negatively correlated in M-EAT, resulting in a positive correlation between EAT fibrosis and the ratio of central to marginal adipocyte diameter (C/M diameter ratio; r = 0.73, P < .01). The C/M diameter ratio was greater in patients with persistent AF than in those with paroxysmal AF. CT images demonstrated that the %change in EAT fat attenuation was positively correlated with EAT fibrosis.ConclusionOur results suggest that the central-to-marginal adipocyte diameter ratio is tightly associated with fibrotic remodeling of EAT. In addition, the %change in EAT fat attenuation determined using CT imaging can detect remodeling noninvasively.

Effect of metformin on epicardial adipose tissue in patients with coronary artery disease without diabetes: A cardiac MRI substudy of the MET-remodel trial

Epicardial adipose tissue (EAT) is a risk factor implicated in the pathogenesis and prognosis of cardiovascular disease. Metformin has been shown to regress EAT in animal models and observational studies. In this study, we report that metformin has no effect on EAT in patients with coronary artery disease without diabetes. • Epicardial adipose tissue is associated with the pathogenesis and prognosis of cardiovascular disease. • Metformin exhibits cardioprotective effects including anti-inflammatory properties. • Metformin treatment has no effect on epicardial adipose tissue compared with placebo in patients with coronary artery disease without type 2 diabetes.

The impact of epicardial adipose tissue in patients with acute myocardial infarction

AimsEpicardial adipose tissue (EAT) has been linked to impaired reperfusion success after percutaneous coronary intervention (PCI). Whether EAT predicts myocardial damage in the early phase after acute myocardial infarction (MI) is unclear. Therefore, we investigated whether EAT in patients with acute MI is associated with more microvascular obstruction (MVO), greater ST-deviation, larger infarct size and reduced myocardial salvage index (MSI).Methods and resultsThis retrospective analysis of a prospective observational study including patients with acute MI (n = 54) undergoing PCI and 12 healthy matched controls. EAT, infarct size and MSI were analyzed with cardiac magnetic resonance imaging, conducted 3–5 days and 12 weeks after MI. Patients with acute MI showed higher EAT volume than healthy controls (46 [25.;75. percentile: 37;59] vs. 24 [15;29] ml, p < 0.001). The high EAT group (above median) showed significantly more MVO (2.22 [0.00;5.38] vs. 0.0 [0.00;2.18] %, p = 0.004), greater ST-deviation (0.38 [0.22;0.55] vs. 0.15 [0.03;0.20] mV×10−1, p = 0.008), larger infarct size at 12 weeks (23 [17;29] vs. 10 [4;16] %, p < 0.001) and lower MSI (40 [37;54] vs. 66 [49;88] %, p < 0.001) after PCI than the low EAT group. After accounting for demographic characteristics, body-mass index, heart volume, infarct location, TIMI-flow grade as well as apnea–hypopnea index, EAT was associated with infarct size at 12 weeks (B = 0.38 [0.11;0.64], p = 0.006), but not with MSI.ConclusionsPatients with acute MI showed higher volume of EAT than healthy individuals. High EAT was linked to more MVO and greater ST-deviation. EAT was associated with infarct size, but not with MSI.Graphic abstract

Imbalance in thioredoxin system activates NLRP3 inflammasome pathway in epicardial adipose tissue of patients with coronary artery disease

Atherosclerosis is the leading cause of death worldwide and has in part an inflammatory basis. Since epicardial adipose tissue (EAT) is in close contact with coronary arteries we hypothesized that an imbalance in thioredoxin-1 (TRX-1) and thioredoxin interacting protein (TXNIP) in EAT, activates NLRP3 inflammasome and promotes production of IL-1β, leading to the development of atherosclerosis. Thirty-eight patients with coronary artery disease (CAD) and thirty patients with no clinical signs of atherosclerosis who underwent open-heart surgery for valve replacement were classified as CAD and control groups, respectively. Biopsy samples from EAT were collected and expression of TXNIP, TRX-1, NLRP3 and IL-1β genes were assessed using qRT-PCR. Tissue protein levels of TXNIP and TRX-1 were determined by Western blotting while ELISA was applied to measure IL-1β. Haematoxylin and eosin staining was used for histological examination. mRNA and protein levels of TXNIP in EAT were significantly higher in patients with CAD compared with control group, whereas CAD patients showed lower TRX-1 gene and protein expression. In addition, in CAD patients the NLRP3 gene expression was almost doubled and IL-1β significantly increased at the both mRNA and protein levels. Enhancment in NLRP3 gene expression and TXNIP protein levels were accompanied with the increase in IL-1β protein level whereas TRX-1 protein content showed a negative correlation with IL-1β level. Concurrent increase in TXNIP, NLRP3, and IL-1β suggests possible involvement of thioredoxin system in the activation of NLRP3 inflammasome, production of IL-1β, and the presence of inflammation in CAD patients.

LncRNA expression profiles and associated ceRNA network analyses in epicardial adipose tissue of patients with coronary artery disease

Epicardial adipose tissue (EAT) contributes to the pathophysiological process of coronary artery disease (CAD). The expression profiles of long non-coding RNAs (lncRNA) in EAT of patients with CAD have not been well characterized. We conducted high-throughput RNA sequencing to analyze the expression profiles of lncRNA in EAT of patients with CAD compared to patients without CAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were executed to investigate the principal functions of the significantly dysregulated mRNAs. We confirmed a dysregulated intergenic lncRNA (lincRNA) (LINC00968) by real-time quantitative PCR (RT-qPCR). Subsequently, we constructed a ceRNA network associated with LINC00968, which included 49 mRNAs. Compared with the control group, lncRNAs and genes of EAT in CAD were characterized as metabolic active and pro-inflammatory profiles. The sequencing analysis detected 2539 known and 1719 novel lncRNAs. Then, we depicted both lncRNA and gene signatures of EAT in CAD, featuring dysregulation of genes involved in metabolism, nuclear receptor transcriptional activity, antigen presentation, chemokine signaling, and inflammation. Finally, we identified a ceRNA network as candidate modulator in EAT and its potential role in CAD. We showed the expression profiles of specific EAT lncRNA and mRNA in CAD, and a selected non-coding associated ceRNA regulatory network, which taken together, may contribute to a better understanding of CAD mechanism and provide potential therapeutic targets.Trial registration Chinese Clinical Trial Registry, No. ChiCTR1900024782.