Pericardial Adipose Research Articles

Unique Genetic and Histological Signatures of Mouse Pericardial Adipose Tissue.

Obesity is a major risk factor for a plethora of metabolic disturbances including diabetes and cardiovascular disease. Accumulating evidence is showing that there is an adipose tissue depot-dependent relationship with obesity-induced metabolic dysfunction. While some adipose depots, such as subcutaneous fat, are generally metabolically innocuous, others such as visceral fat, are directly deleterious. A lesser known visceral adipose depot is the pericardial adipose tissue depot. We therefore set out to examine its transcriptional and morphological signature under chow and high-fat fed conditions, in comparison with other adipose depots, using a mouse model. Our results revealed that under chow conditions pericardial adipose tissue has uncoupling-protein 1 gene expression levels which are significantly higher than classical subcutaneous and visceral adipose depots. We also observed that under high-fat diet conditions, the pericardial adipose depot exhibits greatly upregulated transcript levels of inflammatory cytokines. Our results collectively indicate, for the first time, that the pericardial adipose tissue possesses a unique transcriptional and histological signature which has features of both a beige (brown fat-like) but also pro-inflammatory depot, such as visceral fat. This unique profile may be involved in metabolic dysfunction associated with obesity.

Pericardial adipose tissue is an independent risk factor of coronary artery disease and is associated with risk factors of coronary artery disease

ObjectivePericardial adipose tissue volume (PATV) is related to the mechanism of coronary artery disease (CAD), but its association with CAD risk factors is not clear. This study aimed to investigate the relationships between PATV and its associated factors.MethodsA total of 682 inpatients were consecutively enrolled in this study. Patients were divided into the high PATV group (PATV ≥174.5 cm3; n = 506) and low PATV group (PATV < 174.5 cm3; n = 176). Multiple linear regression analysis was conducted to evaluate the related factors of PATV. Multivariable logistic regression was used to analyze the risk factors of CAD.ResultsLeft ventricular fat volume, right ventricular fat volume, body mass index, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were significant and independent risk factors of enlargement of PATV. Increased PATV was identified as an independent risk factor of CAD, and increased pulse pressure was also independently and positively correlated with CAD.ConclusionsPATV is significantly correlated with the classic risk factors of CAD. Pulse pressure is also correlated with PATV. PATV is an independent risk factor of CAD, and pericardial adipose tissue may alternatively be used in non-invasive diagnostic examination of CAD.

BMPER is upregulated in obesity and seems to have a role in pericardial adipose stem cells.

Pericardial adipose tissue (PAT), a visceral fat depot enveloping the heart, is an active endocrine organ and a source of free fatty acids and inflammatory cytokines. As in other fat adult tissues, PAT contains a population of adipose stem cells; however, whether these cells and/or their environment play a role in physiopathology is unknown. We analyzed several stem cell-related properties of pericardial adipose stem cells (PSCs) isolated from obese and ex-obese mice. We also performed RNA-sequencing to profile the transcriptional landscape of PSCs isolated from the different diet regimens. Finally, we tested whether these alterations impacted on the properties of cardiac mesoangioblasts isolated from the same mice. We found functional differences between PSCs depending on their source: specifically, PSCs from obese PSC (oPSC) and ex-obese PSC (dPSC) mice showed alterations in apoptosis and migratory capacity when compared with lean, control PSCs, with increased apoptosis in oPSCs and blunted migratory capacity in oPSCs and dPSCs. This was accompanied by different gene expression profiles across the cell types, where we identified some genes altered in obese conditions, such as BMP endothelial cell precursor-derived regulator (BMPER), an important regulator of BMP-related signaling pathways for endothelial cell function. The importance of BMPER in PSCs was confirmed by loss- and gain-of-function studies. Finally, we found an altered production of BMPER and some important chemokines in cardiac mesoangioblasts in obese conditions. Our findings point to BMPER as a potential new regulator of PSC function and suggest that its dysregulation could be associated with obesity and may impact on cardiac cells.

B cell subsets in pericardial adipose tissues and their role in cardiovascular health

Abstract We have recently reported that murine pericardial adipose tissues house a large number of lymphoid clusters that have been referred to as fat-associated lymphoid clusters. We have further shown that these tertiary lymphoid tissues are enriched with B cells, in particular B-1a cells. These cells continuously produce a low level of IL-10 under unchallenged conditions, and further enhance the production of this cytokine upon stimulation. Following acute myocardial infarction (MI), these cells significantly expand in pericardial adipose tissues, and they accumulate in the infarcted heart during the resolution phase of MI-induced inflammation where they play a protective role by facilitating the termination of MI-induced inflammation. In our efforts to target B cells for the maintenance of cardiac health, we have now performed a comprehensive characterization of B cell subsets in murine pericardial adipose tissues focusing on cytokines. Using cytokine profiling, RNA sequencing and single-cell RNA sequencing analyses, we have found that subsets of B cells in pericardial adipose tissues are fundamentally biased. Whereas B-2 cells are equipped to produce more pro-inflammatory cytokines, B-1a cells are biased towards producing anti-inflammatory cytokines. These results have paved our way in designing effective therapeutic strategy to target subsets of B cells for the treatment of cardiovascular diseases.

Obesity and psychosocial stress influence the remodelling of pericardial adipose tissue

In obesity, fat is deposited at different sites around the body, but pericardial fat has been shown to have a particularly negative impact on the heart. Very little is known about the function of pericardial fat and how its phenotype is influenced by obesity. The aim of this study was to determine how obesity and stress affects the pericardial phenotype relative to visceral adipose tissue.Here we have used the obese Zucker rat (fa/fa) model induced by a mutation in the leptin receptor. Zucker rats develop hyperphagia with reduced energy expenditure, resulting in morbid obesity; impaired glucose and insulin sensitivity in a few weeks after birth. At 9 weeks of age lean (LZR) and obese (OZR) Zucker male rats were treated with or without unpredictable chronic mild stress (UCMS) for 8 weeks to mimic human clinical stress and depression. Adipose tissue can expand either through cellular hypertrophy or hyperplasia, with the former correlating with decreased metabolic health in obesity. To determine the phenotype for pericardial and visceral adipose tissue, tissue cellularity and gene expression were analysed. Tissue cellularity was determined following Haematoxylin and Eosin (H&amp;E) staining, whilst qPCR was used to examine gene expression.Data from these experiments showed that, as expected, the OZR group were considerably heavier than the lean controls (LZR). Total plasma corticosterone and glucose all increased in the obese group indicating that obesity in itself increases stress. Furthermore, UCMS stress conditions had an additive effect by increasing these parameters further in both the lean LZR and the obese OZR group indicating that stress had a negative metabolic impact.H&amp;E staining showed that there was greater heterogeneity in the cellularity of pericardial adipocytes compared with visceral adipose tissue, suggesting a mix of white, beige and brown‐like adipocytes. Analysis of tissue cellularity showed that obesity did not result in a significant alteration in adipocyte cell size in pericardial fat. However, when UCMS was combined with obesity there was a significant increase in adipocyte cell size relative to the lean group. This suggests that under non‐stressful conditions, pericardial adipose tissue does not expand predominantly through hypertrophy, unlike visceral adipocytes. However, stressful conditions combine with obesity to produce a more pathological pericardial adipose tissue phenotype.Gene expression analysis showed that UCMS stress caused an upregulation of leptin in the lean compared with the obese group. This suggests that leptin signalling is important for the stress‐dependent increase in adipose tissue leptin expression. Finally, the thermogenic marker UCP1 was upregulated in pericardial adipose tissue of obese rats relative to the lean controls but not in visceral tissue. These data strongly indicate that there is differential regulation of gene expression between pericardial and visceral adipose tissue which may have major implications for the heart in obesity.Support or Funding InformationUniversity of Reading, UK and the Petroleum Technology Development Fund, Nigeria

Pericardial adipose tissue, cardiac structures, and cardiovascular risk factors in school-age children.

Aims We examined the associations of pericardial adipose tissue with cardiac structures and cardiovascular risk factors in children.Methods and results We performed a cross-sectional analysis in a population-based cohort study among 2892 children aged 10 years (2404 normal weight and 488 overweight/obese). Pericardial adipose tissue mass was estimated by magnetic resonance imaging (MRI) and indexed on height3. Left ventricular mass (LVM) and left ventricular mass-to-volume ratio (LMVR) were estimated by cardiac MRI. Cardiovascular risk factors included android adipose tissue percentage obtained by Dual-energy X-ray absorptiometry, blood pressure and glucose, insulin, cholesterol, and triglycerides concentrations. Adverse outcomes were defined as values above the 75 percentile. Median pericardial adipose tissue index was 3.6 (95% range 1.6–7.1) among normal weight and 4.7 (95% range 2.0–8.9) among overweight children. A one standard deviation (1 SD) higher pericardial adipose tissue index was associated with higher LMVR [0.06 standard deviation scores, 95% confidence interval (CI) 0.02–0.09], increased odds of high android adipose tissue [odd ratio (OR) 2.08, 95% CI 1.89–2.29], high insulin concentrations (OR 1.17, 95% CI 1.06–1.30), an atherogenic lipid profile (OR 1.22, 95% CI 1.11–1.33), and clustering of cardiovascular risk factors (OR 1.56, 95% CI 1.36–1.79). Pericardial adipose tissue index was not associated with LVM, blood pressure, and glucose concentrations. The associations showed largely the same directions but tended to be weaker among normal weight than among overweight children.Conclusion Pericardial adipose tissue is associated with cardiac adaptations and cardiovascular risk factors already in childhood in both normal weight and overweight children.

Abstract MP57: Lactation Duration is Associated With Lower Visceral and Pericardial Fat Volumes in Parous Women: 25-year Follow-up in the Cardia Study

Introduction: Lactation has been associated with a lower risk of incident type 2 diabetes mellitus and cardiovascular disease (CVD) in women. However, the underlying mechanisms for these associations are not well understood. The longitudinal association between lactation and maternal fat volume has rarely been investigated. Hypothesis: We tested the hypothesis that lactation duration is inversely associated with maternal visceral and pericardial fat volumes. Methods: Data were obtained from 910 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study (1985-86) without diabetes prior to pregnancy who had ≥1 birth during 25 years of follow-up. Cumulative lactation duration across all births since baseline was calculated from self-reports collected at each exam. Volumes of visceral and pericardial adipose tissue were measured from computed tomographic scans at the Year 25 exam in 2010-2011. Methods: At baseline, the average age of women (48% black, 52% white) was 24 years (range: 18-30 years). During 25 years of follow-up, 76% of women reported lactation duration of ≥ 1 month. In adjusted linear regression models, lactation duration was inversely associated with visceral fat (p=0.021) and pericardial fat (p=0.001) volumes (Table). There was a significant interaction between race and lactation on visceral (p=0.035) and pericardial fat (p=0.027) volumes (Table). Formal mediation analysis showed a significant indirect effect of lactation duration on visceral (p=0.001) and pericardial fat (p=0.002) volumes through body weight change between the first postbaseline birth and the end of follow-up. Changes in body weight mediated 29.4% and 26.0% of the association between lactation duration and visceral and pericardial fat volumes. Conclusions: In this prospective study, the associations of longer lactation duration with lower visceral and pericardial fat volumes were partially mediated by body weight changes.

CORONARY INFLAMMATION ASSESSED BY PERICORONARY ADIPOSE TISSUE ATTENUATION ON COMPUTED TOMOGRAPHY ANGIOGRAPHY PREDICTS ATRIAL FIBRILLATION RECCURENCE AFTER CRYOBALLOON ABLATION

Recent studies reported the association between the prevalence of atrial fibrillation (AF) and pericardial adipose tissue assessed by computed tomography (CT). We investigated the association between pericoronary adipose tissue (PCAT), adipose tissue that directly surrounds the coronary artery, and

Left ventricular myocardial deformation: a study on diastolic function in the Chinese male population and its relationship with fat distribution.

Obesity has become an epidemic in China with its increased prevalence, especially in the male population. Disparities in fat distribution rather than increasing body mass index (BMI) confer the risk of different diseases, including cardiac abnormalities. Therefore, early detection of cardiac abnormalities is important for treatment to reverse the progression to heart failure. Nowadays, strain analysis based on cardiac magnetic resonance (CMR) imaging has been established to assess myocardial function in diverse cardiac diseases. We aimed to assess the relationship between fat distribution and subclinical diastolic dysfunction in obese Chinese men assessed by deformation registration algorithm (DRA)-based myocardial strain rate (SR) analysis. A total of 115 male participants with different BMI underwent CMR scanning using a 1.5T MAGNETOM Aera (Siemens Healthcare, Erlangen, Germany) and computed tomography (CT) scan. All the participants were enrolled from September 2017 to April 2018. They were classified into 3 groups according to their BMIs with 23 and 27.5 kg/m2 being the cutoff values. A Trufi-Strain prototype software (version 2.0, Siemens Healthcare, Erlangen, Germany) was used to quantify SR in both early and late diastole from CMR cine images. Ratios of early and late SRs were calculated. Areas of epicardial and pericardial adipose tissue (EAT and PAT) were measured on a single 4-chamber-view slice of cine images. Volumes of visceral and subcutaneous adipose tissue (VAT and SAT) were acquired semi-automatically from CT images using the dedicated software Cardiac Risk2.0 (Siemens Healthcare). Waist and hip circumferences were manually measured (WC and HC). Analysis of variance or nonparametric tests, along with correlation and stepwise multivariate regression analysis models, was applied for statistical analysis. Peak late diastolic SRs were higher in obese men compared with their lean counterparts [-36.25±10.46 vs. -29.46±8.17, 66.97±18.58 vs. 45.62 (42.44, 55.96), and 56.81±15.07 vs. 41.40±6.41 for radial, circumferential, and longitudinal SRs, respectively; P<0.05]. All SR ratios in the obese subgroups were lower than those of lean men (3.12±1.14 vs. 4.63±1.24, 2.12±0.58 vs. 2.96±0.62 and 1.63±0.50 vs. 2.20±0.63 for radial, circumferential, and longitudinal directions, respectively; P<0.05). EAT was a significant predictor of diastolic function assessed by radial and circumferential SR ratios (β=-0.439 and -0.337 respectively; all P<0.001), while VAT was a significant predictor of circumferential and longitudinal SR ratios (β=-0.216 and -0.355, respectively, P<0.05). Decreased LV diastolic function assessed by DRA-based SR analysis in obesity is associated with fat distribution. Furthermore, EAT and VAT might be better predictors of a decrease of diastolic function in obese Chinese men than BMI.

PERICARDIAL ADIPOSE TISSUE THICKNESS AS AN INDICATOR OF CARDIOVASCULAR RISK

It has been suggested that visceral adipose tissue around the heart might have an important correlation with cardiovascular risk progression. This study's aim is to corroborate pericardial adipose tissue thickness (PATT) as a biomarker of cardiovascular risk. Echocardiographic data including PATT

The Role of Quantitative Assessment of Visceral Adipose Tissue of the Heart as a Predictor for Cardiovascular Events

Objective of this article – to evaluate possibilities to visualize cardiac visceral adipose tissue by echocardiography, computed tomography (CT), and magnetic resonanse imaging (MRI) and to systematize data on its physiological and pathological roles. To achieve this goal, the authors analyzed relevant Russian and foreign sources of literature in the scientific libraries eLIBRARY and PubMed, by using the keywords: “pericardial fat”, “epicardial fat”, “visceral fat of the heart”, “epicardial adipose tissue”, “pericardial adipose tissue”, and “adipocytokine”. Actual data as of November 2018 were collected. The review presents up-to-date data on the physiological and pathophysiological roles of cytokines secreted by pericardial adipose tissue, as well as on correlations and possible theories of the relationship between the volumes of pericardial adipose tissue and the development of coronary heart disease, atrial fibrillation, and metabolic syndrome. According to echocardiography, epicardial adipose tissue thickness is a reliable predictor for the presence of high-risk atherosclerotic plaques in the coronary arteries. Adipose tissue volume can be measured with high accuracy using CT (manual, semi-automatic, and automatic methods).A number of studies prove that MRI can be used for assigned tasks. The current notion of the role of these adipose depots can potentially be used in assessing the risk of cardiovascular diseases. The literature review presented confirms that visceral adipose tissue of the heart has a direct effect on the myocardium and coronary arteries and can be quantified using echocardiography, CT and MRI.

Effect of 5-lipoxygenase inhibitor, VIA-2291 (Atreleuton), on epicardial fat volume in patients with recent acute coronary syndrome

Background and aimsThe association between inflammation and atherosclerosis has been well described in the literature. There is now mounting evidence in support of adipose tissue as a reservoir for inflammatory markers. Epicardial adipose tissue (EAT) has been shown to associate with coronary atherosclerosis and found to be a predictor of future adverse cardiovascular events. This study, VIA-EAT, assesses the change in epicardial fat volume (EFV) after treatment with an investigational anti-inflammatory agent (VIA-2291) in a cohort of post-acute coronary syndrome (ACS) patients. MethodsThis study is derived from a post-hoc analysis of a previously conducted randomized clinical trial (NCT00358826). Patients were recruited for a prospective, double-blind, multi-center randomized trial of a 5-lipooxygenase inhibitor or placebo in a 3:1 randomization, including doses of placebo, and 25 mg, 50 mg and 100 mg of active treatment. Cardiac computed tomography was performed at baseline and at 24 weeks after treatment with VIA-2291. EAT and pericardial adipose tissue (PAT) were measured using previously published methodology. A Pearson correlation test was used to determine the relationship between change in epicardial fat and change in plaque composition. ResultsWe analyzed 54 pre- and post-treatment scans. There were no major differences between traditional cardiovascular risk factors among the 4 randomized study arms. There was a significant decrease in EAT and PAT in patients in the treatment arms vs. placebo, −3.0 ± 8.2mm3 and −3.9 ± 10.9mm3 vs. 1.7 ± 7.5mm3 and 1.4 ± 10.7mm3 (p = 0.001), respectively. The changes in EAT and PAT were more pronounced in patients taking 100 mg of the drug vs. placebo: 4.2 ± 9.6mm3, -7.6 ± 8.5mm3, p = 0.0001, respectively. In a subgroup analysis, reduction in epicardial fat volume correlated with reduction in total atherosclerotic plaque volume across all VIA treatment groups, r = 0.52 (p = 0.004). ConclusionsAfter adjustment for traditional cardiovascular risk factors including age, gender, body mass index, dyslipidemia and smoking, VIA-2291 decreases EAT and PAT in individuals with recent ACS. Treatment with the drug also appears to alter plaque volume and composition.

1100 When multimodality imaging is needed to understand the etiology of diffuse negative t waves

Abstract Introduction We present the case of a 50 year old woman, active smoker, hypercholesterolemic, nondiabetic, with normal body mass index, referred to our cardiology department for atypical chest pain and ECG changes (diffuse negative T waves in V1-V6, DII, DIII) (Panel A), also present on a resting ECG recorded 4 years previously. Purpose To highlight the fact that even though the most frequent cause of negative T waves remains coronary artery disease (CAD), the cause could be related to other more rare medical conditions. Methods After clinical examination and ECG, 2D echocardiography was performed. It revealed a normal sized left ventricle (LV) with perserved global and regional function, normal global longitudinal strain, nondilated atria and no significant valvular disease. The subcostal view suggested a hypertrophied right ventricle (RV) free wall (10 mm thickness, with apparent homogeneous echogenicity) (Panel B, arrow), with normal longitudinal function and no regional wall motion abnormalities. Cardiac magnetic resonance (CMR) was performed for a better tissue characterization. The CMR examination found normal cardiac cavities, normal wall thickness of both ventricles (RV free wall of 3 mm), no late gadolinium enhancement, but described a large amount of fat with concentric disposition, maximum thickness of 9 mm anterior of RV, 3 mm posterior of LV (Panel C). Since this was not fully explaining the ECG changes and the patient presented with a low-intermediate pretest probability for CAD, an angio-CT coronary scan was performed and showed a calcium score of 7 AU, no significant coronary atherosclerosis, and a hypoplastic circumflex artery (Panel D, arrow). A total volume of 149 ml. of pericardial fat was measured (Panel E). Stress echocardiography was performed with maximal workload achieved (145 bpm, 85% predicted, 100 W); no chest pain was reported, no regional wall motion abnormalities were seen and there was normal contractile reserve. Results Using multimodality imaging a differential diagnosis was followed, which included: arrhythmogenic cardiomyopathy (negative T waves, apparent changes of RV free wall on echo, but no family history of sudden cardiac death), CAD (atypical angina, cardiovascular risk factors, negative T waves), and pericarditis (but negative inflammatory markers, no pericardial fluid). The final hypothesis is that the ECG changes are related to the abnormal pericardial adipose tissue deposit, which acts similar to pericarditis. Conclusions The present case report is, to our knowledge, the first to describe an association between large pericardial fat deposit and ECG changes, when other causes were excluded. Even if the current findings are benign, the patient should be followed closely, and risk factors should be thoroughly controlled, as several studies have shown that pericardial fat is associated with poorer cardiovascular prognosis Abstract 1100 Figure. Multimodality imaging in our patient

Epicardial adipose tissue: an emerging biomarker of cardiovascular complications in type 2 diabetes?

Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease and heart failure, which highlights the need for improved understanding of factors contributing to the pathophysiology of these complications as they are the leading cause of mortality in T2D. Patients with T2D have high levels of epicardial adipose tissue (EAT). EAT is known to secrete inflammatory factors, lipid metabolites, and has been proposed to apply mechanical stress on the cardiac muscle that may accelerate atherosclerosis, cardiac remodeling, and heart failure. High levels of EAT in patients with T2D have been associated with atherosclerosis, diastolic dysfunction, and incident cardiovascular events, and this fat depot has been suggested as an important link coupling diabetes, obesity, and cardiovascular disease. Despite this, the predictive potential of EAT in general, and in patients with diabetes, is yet to be established, and, up until now, the clinical relevance of EAT is therefore limited. Should this link be established, importantly, studies show that this fat depot can be modified both by pharmacological and lifestyle interventions. In this review, we first introduce the role of adipose tissue in T2D and present mechanisms involved in the pathophysiology of EAT and pericardial adipose tissue (PAT) in general, and in patients with T2D. Next, we summarize the evidence that these fat depots are elevated in patients with T2D, and discuss whether they might drive the high cardiometabolic risk in patients with T2D. Finally, we discuss the clinical potential of cardiac adipose tissues, address means to target this depot, and briefly touch upon underlying mechanisms and future research questions.

P376 Epicardial to pericardial adipose tissue ratio: predicting ischemic etiology of left ventricular systolic dysfunction

Abstract Background Epicardial adipose tissue (EPI) and pericardial adipose tissue (PERI) measured using echocardiography or magnetic resonance imaging have shown to be markers of metabolic syndrome and begin to be regarded as predictors of coronary artery disease. EPI is also thought to have paracrine effects on coronary vessels and, therefore, might be more intimately linked to ischemic heart disease. Purpose We aim to study if EPI related to PERI thickness is a predictor of ischemic etiology of left ventricular (LV) systolic dysfunction among ambulatory patients. Methods We retrospectively evaluated 56 consecutive patients followed on a heart failure clinic. A cardiologist, blind to the clinical records and systolic dysfunction etiology, reviewed the echocardiographic images and measured EPI and PERI thickness on right ventricle free wall (parasternal long axis view). Cardiovascular risk factors, body mass inex (BMI), LV dimensions by echo, LV systolic dysfunction etiology (investigated by other means such as angiography or magnetic resonance) were analyzed. Results Echocardiographic image quality allowed for analyzing 55 patients (80% male, 62% hypertension, 51% diabetes, 44% dyslipidemia, BMI 28,9 ± 4,0, age 66 ± 14 years). Mean EPI thickness was 3,4 ± 2,0 mm and PERI was 5,6 ± 3,4 mm. LV ejection fraction 33 ± 10% and LV end diastolic volume 157 ± 48ml. Supplementary investigations showed an ischemic etiology of LV systolic dysfunction in 45% of patients. We found that patients with EPI thickness equal or greater than PERI were more likely to have an ischemic etiology (univariate analysis: OR 9,8 p = 0,002; adjusted for BMI and diabetes: OR 5,8 p = 0,032). Conclusions Epicardial adipose tissue thickness equal or greater than pericardial adipose tissue, parameter easily obtained using transthoracic echocardiography, may predict ischemic etiology of LV systolic dysfunction in a cohort of ambulatory patients . Future research will be necessary to confirm this finding and its possible value in every-day clinical practice as marker of coronary artery disease. ALL ISCHEMIC NON ISCHEMIC p Epicardial Adipose Tissue 3,4 ± 2,0 3,7 ± 1,6 3,1 ± 2,2 0,53 Pericardial Adipose Tissue 5,6 ± 3,4 4,6 ± 3,0 6,4 ± 3,5 0,09 Ratio EPI/PERI 0,82 ± 0,66 1,16 ± 0,83 0,55 ± 0,28 0,000 Table Adipose tissue thickness measured on paraesternal long axis (mm): mean ± SD.

P2Y2 Nucleotide Receptor Is a Regulator of the Formation of Cardiac Adipose Tissue and Its Fat-Associated Lymphoid Clusters.

The formation of pericardial adipose tissue (PAT) and its regulatory function in cardiac inflammation are not well understood. We investigated the potential role of the ubiquitous ATP/UTP nucleotide receptor P2Y2 in the PAT by using P2Y2-null mice. We observed that P2Y2-null mice displayed a lower mass of PAT and a reduced density of its fat-associated lymphoid clusters (FALCs) and, more particularly, B cells. Loss of P2Y2 receptor in pericardial preadipocytes decreased their adipogenic differentiation and maturation abilities in vitro. Gene profiling identified P2Y2 target genes in PAT linked to immunomodulation. These data led to the identification of an increase of M2c anti-inflammatory macrophages correlated with increased apoptosis of B lymphocytes in P2Y2-null pericardial fat. In addition, follicular helper T cells, which contribute to B cell expansion in germinal centers, were dramatically decreased. The effect of P2Y2 loss was also investigated after ischemia-mediated expansion of FALCs in a model of myocardial infarct. Loss of P2Y2 led to reduced expansion of B and neutrophil populations in these clusters, whereas density of M2c anti-inflammatory macrophages was increased. Our study defines the P2Y2 nucleotide receptor as a regulator of the formation and inflammatory status of pericardial fat. The P2Y2 receptor could represent a therapeutic target in the regulation of PAT function before and during cardiac ischemia.

Relationships between visceral/subcutaneous adipose tissue FABP4 expression and coronary atherosclerosis in patients with metabolic syndrome.

Cytoplasmic fatty acid-binding proteins facilitate the transport of lipids to specific compartments in cells. Fatty acid-binding protein 4 (FABP4), also known as aP2 or A-FABP, plays a key role in the development of atherosclerosis, insulin resistance, obesity, and metabolic syndrome (MS). The FABP4 polymorphisms are associated with protein expression changes invitro and metabolic and vascular alterations invivo. The aim of this study was to investigate the association between FABP4 messenger ribonucleic acid (mRNA) expression levels in epicardial (EAT), pericardial (PAT), and subcutaneous adipose tissues (SAT), and the extent of coronary atherosclerosis in coronary artery disease (CAD) patients with MS. Furthermore, the relationship between the extent of coronary atherosclerosis and epicardial adipose tissue volume (EATV) and FABP4 gene variations was evaluated. A total of 37 patients undergoing coronary artery bypass grafting because of CAD (MS CAD group) and 23 non-MS patients undergoing heart valve surgery (control group) were included. Coronary angiography was performed for all patients and the extent of coronary atherosclerosis was assessed using the Sullivan's scoring system. The mRNA expression levels of FABP4 gene in EAT, PAT, and SAT, and FABP4 polymorphisms were analyzed using the quantitative real-time polymerase chain reaction (qRT-PCR). An increased FABP4 expression was observed in EAT and PAT of MS CAD group compared to controls. In the MS CAD group, FABP4 mRNA expression levels in EAT was 2.8-fold highercompared to PAT. The expression of FABP4 in EAT was positively correlated with the extent of atherosclerosis and EATV in MS CAD group (r=0.588, P=0.001, r=0.174, P=0.001, respectively). There were no correlations between PAT and SAT versus the extent of atherosclerosis and EATV. The FABP4 EAT mRNA expression levels were found to significantly increase in mutant allele carriers of rs1054135, whereas they significantly decreased in mutant allele carriers of rs77878271 (T-87C) in MS CAD group (P<0.05). The extent of atherosclerosis was also found to be significantly associated with rs1054135 (P<0.05). A cut-off point of 57.5cm3 EATV was used indicating the presence of CAD with a significant area under the curve of 0.783%, 98% sensitivity, and 100% specificity (95% CI 0.620-0.880; P<0.05). Our study results suggest that FABP4 expression in EAT is strongly associated with the extent of atherosclerosis and EATV in MS CAD patients.

Cardiac MRI measurements of pericardial adipose tissue volumes in patients on in-centre nocturnal hemodialysis.

Conversion from conventional hemodialysis (CHD) to in-centre nocturnal hemodialysis (INHD) is associated with left ventricular (LV) mass regression, but the underlying mechanisms are not fully understood. Using cardiac MRI (CMR), we examined the effects of INHD on epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT), and the relationships between EAT, PAT and LV remodeling, biomarkers of nutrition, myocardial injury, fibrosis and volume. We conducted a prospective multicenter cohort study of 37 patients transitioned from CHD to INHD and 30 patients on CHD (control). Biochemical markers and CMR were performed at baseline and 52weeks. CMR images were analyzed by independent readers, blinded to order and treatment group. Among 64 participants with complete CMR studies at baseline (mean age 54; 43% women), there were no significant differences in EAT index(60.6 ± 4.3mL/m2 vs 64.2 ± 5.1mL/m2, p = 0.99) or PATindex (60.0 ± 5.4mL/m2 vs 53.2 ± 5.9mL/m2, p = 0.42) between INHD and CHD groups. Over 52weeks, EATindex and PAT indexdid not change significantly in INHD and CHD groups (p = 0.21 and 0.14, respectively), and the changes in EATindex and PATindex did not differ significantly between INHD and CHD groups (p = 0.30 and 0.16, respectively). Overall, changes in EAT indexinversely correlated with changes in LV end-systolic volume index (LVESVI) but not LV end-diastolic volume index (LVEDVI), LV mass index (LVMI), and LV ejection fraction (LVEF). Changes in PATindex inversely correlated with changes in LVESVI, LVMI and positively correlated with changes in LVEF. There were no correlations between changes in EAT indexor PAT indexwith changes in albumin, LDL, triglycerides, troponin-I, FGF-23, or NT-proBNP levels over 52weeks (all p > 0.30). INHD was not associated with any changes in EATindex and PATindex over 12months. Changes in EATindex were not significantly associated with changes in markers of LV remodeling, nutrition, myocardial injury, fibrosis, volume status. In contrast, changes in PATindex, which paradoxically is expected to exert less paracrine effect on the myocardium, were correlated with changes in LVESVI, LVMI and LVEF. Larger and longer-term studies may clarify the role of PAT in cardiac remodeling with intensified hemodialysis. CLINICALTRIALS. NCT00718848.

IL-10–producing B cells are enriched in murine pericardial adipose tissues and ameliorate the outcome of acute myocardial infarction

Acute myocardial infarction (MI) provokes an inflammatory response in the heart that removes damaged tissues to facilitate tissue repair/regeneration. However, overactive and prolonged inflammation compromises healing, which may be counteracted by antiinflammatory mechanisms. A key regulatory factor in an inflammatory response is the antiinflammatory cytokine IL-10, which can be produced by a number of immune cells, including subsets of B lymphocytes. Here, we investigated IL-10-producing B cells in pericardial adipose tissues (PATs) and their role in the healing process following acute MI in mice. We found that IL-10-producing B cells were enriched in PATs compared to other adipose depots throughout the body, with the majority of them bearing a surface phenotype consistent with CD5+ B-1a cells (CD5+ B cells). These cells were detected early in life, maintained a steady presence during adulthood, and resided in fat-associated lymphoid clusters. The cytokine IL-33 and the chemokine CXCL13 were preferentially expressed in PATs and contributed to the enrichment of IL-10-producing CD5+ B cells. Following acute MI, the pool of CD5+ B cells was expanded in PATs. These cells accumulated in the infarcted heart during the resolution of MI-induced inflammation. B cell-specific deletion of IL-10 worsened cardiac function, exacerbated myocardial injury, and delayed resolution of inflammation following acute MI. These results revealed enrichment of IL-10-producing B cells in PATs and a significant contribution of these cells to the antiinflammatory processes that terminate MI-induced inflammation. Together, these findings have identified IL-10-producing B cells as therapeutic targets to improve the outcome of MI.

P6429Epicardial adipose tissue is a robust measure of increased risk of myocardial infarction, a meta-analysis on over 6.600 patients

Abstract Background Epicardial adipose tissue surrounds the heart and the coronary arteries. Endocrine and paracrine activity is accredited to EAT. Studies descripted the association between increased EAT and traditional cardiovascular risk factors as well as coronary events. While computed tomography is the gold standard for the assessment of 3-dimensional EAT-volume, echocardiography based EAT thickness is an easy accessible alternative in particular in an emergency setting. So far, little is known, how quantification of EAT in patients presenting with chest pain could alter patient management. Purpose To perform a meta-analysis on existing studies, comparing EAT in patients with and without myocardial infarction, stratifying by imaging technique. Methods We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, describing EAT in patients with and without myocardial infarction. Manuscripts, published until 1st of October 2018, were included. We made our search specific and sensitive using Medical Subject Headings terms and free text and considered studies published in English language. Search terms used were “epicardial adipose tissue” or “pericardial adipose tissue” and “myocardial infarction”, “coronary events”, or “acute coronary syndrome”. For comparability, EAT measures were normalized to mean values for patients without myocardial infarction for each study separately. Random effect models were calculated. All analyses were performed using Review Manager 5.3. Results Overall, 6.641 patients (mean aged 58.9 years, 53% male) from 7 studies were included. Patients with myocardial infarction had 37% higher measures of EAT compared to patients without myocardial infarction (95% CI: 21–54%, Figure A). Comparing studies using echocardiography for assessment of EAT thickness with studies using computed tomography based EAT volume, similar relative differences in EAT with wide overlap of confidence intervals were observed (Echo measures: 40 [4–76]%, CT measures: 36 [16–57]%, Figure B and C). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown). Figure 1 Conclusion EAT is increased in patients with myocardial infarction. Our data suggests that quantification of EAT thickness using echocardiography distinguishes equally between patients with and without myocardial infarction as compared to 3-dimensional EAT volume from computed tomography. Therefore, it may be an easy accessible alternative in clinical settings. However, further studies are warranted to determine, whether quantification of EAT may lead to improved patient management.