Mediastinal Adipose Tissue Research Articles

Hepatic steatosis is associated with abnormal hepatic enzymes, visceral adiposity, altered myocardial glucose uptake measured by 18F-FDG PET/CT

BackgroundNonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects the liver and a variety of extra-hepatic organ systems. This study aimed to investigate the relationship between hepatic steatosis and glucose metabolism in liver and extra-hepatic tissues and organs.MethodsThe whole body 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) images of 191 asymptomatic tumor screening patients were retrospectively analyzed. Patients with the ratio of spleen/liver CT densities > 1.1 were defined to have NAFLD, and their clinical symptoms, laboratory markers, FDG uptake in a variety of tissues and organs including heart, mediastinal blood pool, liver, spleen, pancreas, and skeletal muscle, as well as abdominal adipose tissue volumes including visceral adipose tissue (VAT) volume and subcutaneous adipose tissue (SAT) volume were compared with those of the non-NAFLD patients and used to analyze the independent correlation factors of NAFLD.ResultsAmong the 191 patients, 33 (17.3%) were NAFLD, and 158 (82.7%) were non-NAFLD. There was no significant correlation between the mean standardized uptake value (SUVmean) and CT density of liver as well as the ratio of spleen/liver CT densities. Hepatic steatosis, but not FDG intake, was more significant in NAFLD patients with abnormal liver function than those with normal liver function. Compared with the non-NAFLD patients, NAFLD patients had significantly reduced myocardial glucose metabolism, but significantly increased mediastinal blood pool, spleen SUVmean and abdominal adipose tissue volumes (including VAT and SAT volumes) (P < 0.05). Multivariate regression analysis showed that elevated serum ALT, increased abdominal VAT volume, and decreased myocardial FDG uptake were independent correlation factors for NAFLD. Further studies showed that hepatic steatosis and myocardial FDG uptake were mildly linearly correlated (r = 0.366 with hepatic CT density and − 0.236 with the ratio of spleen/liver CT densities, P < 0.05).ConclusionsNAFLD is a systemic disease that can lead to the change of glucose metabolism in some extra-hepatic tissues and organs, especially the myocardium.

CD4 and CD8 double positive T cell progenitors in mediastinal adipose tissue and the aortic arch differentiate to CD4 T cells

Abstract Using 10× Genomics-based single-cell RNA sequencing on digested atherosclerotic mouse aortas, we discovered an unexpected immune cell population whose transcriptome was similar to thymic CD4+CD8+ cells (DPs). Flow cytometry showed DP presence in the aortic arch (AA) and mediastinal adipose tissue (MAT), but not in lymph nodes, spleen, blood or other tissues. DPs in MAT or AA did not change with atherosclerosis in Apoe−/− mice. Fluorescence microscopy of cleared whole mounts placed DPs in the AA adventitia and near microvessels in MAT. MAT and AA DPs were absent in Rag2−/− mice and in day3 and 21 thymectomized mice. Deep transcriptional profiling from sorted thymic, MAT, and AA DPs showed hundreds of differentially expressed genes. While thymic DPs were enriched for TCR signaling pathways, extra-thymic DPs were enriched for stress responses and cell cycle pathways. Pulse-chase experiments demonstrated a five-day turnover of MAT and AA DPs. Functionally, sorted MAT DPs developed successfully into conventional T cells (with a bias to CD4) in hanging drop cultures. Pharmacologic inhibition of cell migration by S1P1 blockage with FTY720 did not affect the presence of these cells, suggesting that migration of extra-thymic DPs does not require passage into blood. Transplantation of congenically marked thymi under the kidney capsule of thymectomized mice reconstituted T cells in the inguinal lymph node, but failed to reconstitute extra-thymic DPs. The discovery of two new, transcriptionally distinct subsets of extrathymic DPs reveals a novel, unexpected local escape mechanism from the thymus. Their association with blood vessels suggests possible angiotrophic functions.

Epicardial adipose tissue volume and annexin A2/fetuin-A signalling are linked to coronary calcification in advanced coronary artery disease: Computed tomography and proteomic biomarkers from the EPICHEART study

Background & aimsThe role of epicardial adipose tissue (EAT) in the pathophysiology of late stage-coronary artery disease (CAD) has not been investigated. We explored the association of EAT volume and its proteome with advanced coronary atherosclerosis. MethodsThe EPICHEART Study prospectively enrolled 574 severe aortic stenosis patients referred to cardiac surgery. Before surgery, EAT volume was quantified by computed tomography (CT). During surgery, epicardial, mediastinal (MAT) and subcutaneous (SAT) adipose tissue samples were collected to explore fat phenotype by analyzing the proteomic profile using SWATH-mass spectrometry; pericardial fluid and peripheral venous blood were also collected. CAD presence was defined as coronary artery stenosis ≥50% in invasive angiography and by CT-derived Agatston coronary calcium score (CCS). ResultsEAT volume adjusted for body fat was associated with higher CCS, but not with the presence of coronary stenosis. In comparison with mediastinal and subcutaneous fat depots, EAT exhibited a pro-calcifying proteomic profile in patients with CAD characterized by upregulation of annexin-A2 and downregulation of fetuin-A; annexin-A2 protein levels in EAT samples were also positively correlated with CCS. We confirmed that the annexin-A2 gene was overexpressed in EAT samples of CAD patients and positively correlated with CCS. Fetuin-A gene was not detected in EAT samples, but systemic fetuin-A was higher in CAD than in non-CAD patients, suggesting that fetuin-A was locally downregulated. ConclusionsIn an elderly cohort of stable patients, CCS was associated with EAT volume and annexin-A2/fetuin-A signaling, suggesting that EAT might orchestrate pro-calcifying conditions in the late phases of CAD.

WS05.04 Particularities of Lymphadenectomy in Malignant Pleural Mesothelioma

WS05.04 Particularities of Lymphadenectomy in Malignant Pleural Mesothelioma

UCP1 expression-associated gene signatures of human epicardial adipose tissue.

Multiple reports of uncoupling protein 1 (UCP1) expression have established its presence in human epicardial adipose tissue (eAT). Its functional relevance to eAT, however, remains largely unknown. In a recent study, we reported that adrenergic stimulation of eAT was associated with downregulation of secreted proteins involved in oxidative stress-related and immune-related pathways. Here, we explored the UCP1-associated features of human eAT using next-generation deep sequencing. Paired biopsies of eAT, mediastinal adipose tissue (mAT), and subcutaneous adipose tissue (sAT) obtained from cardiac surgery patients, with specific criteria of high and low expression of UCP1 in eAT, were subjected to RNA sequencing. Although eAT exhibited a depot-specific upregulation in the immune-related pathways relative to mAT and sAT, high UCP1 expression in eAT was specifically associated with differential gene expression that functionally corresponded with downregulation in the production of reactive oxygen species and immune responses, including T cell homeostasis. Our data indicate that UCP1 and adaptive immunity share a reciprocal relationship at the whole-transcriptome level, thereby supporting a plausible role for UCP1 in maintaining tissue homeostasis in human eAT.

Reduction of plasma angiopoietin‐like 2 after cardiac surgery is related to tissue inflammation and senescence status of patients

IntroductionA strong positive relationship has been reported in humans between high levels of circulating angiopoietin‐like 2 (ANGPTL2), a pro‐inflammatory adipokine, and cardiovascular diseases (CVD). ANGPTL2 levels can predict the incidence of CVD, but whether a cardiac surgery such as a coronary artery bypass graft (CABG), aortic valve replacement or both, is able to modulate ANGPTL2 levels is unknown.HypothesisCardiac surgery alleviates cardiac stress and lowers ANGPTL2 circulating levels.MethodsIn patients undergoing CABG (n=16), valve replacement (n=16), or both (n=15), blood was taken before surgery and 24h, 4±1 days (hospital discharge) and 60±30 days (follow‐up visit) post‐surgery to quantify plasma levels of ANGPTL2 and plasma hs‐CRP levels. Mediastinal adipose tissue (MAT) and internal mammary fragments (IMA) were dissected out during surgery, RNA extracted and gene expression assessed by quantitative RT‐PCR.ResultsThe type of surgery had no impact on the overall profile of plasma ANGPTL2 or hs‐CRP levels post‐surgery. Both markers rose transiently after 24h and returned progressively to baseline levels. However, we observed two different patterns for ANGPTL2: compared to basal values, levels either decreased in 45% (DECREASED group, n=21) or increased in 55% (INCREASED group, n=26) of the patients at the end of the follow‐up (p&lt;0.001). In contrast, hs‐CRP levels were identical between these two groups (p=0.9967). Patients in the INCREASED group were 8 years older (p=0.002), had a higher systolic blood pressure (p=0.038), and they received 20 times more (p&lt;0.0001) noradrenaline 24h after the surgery, suggesting a higher inflammatory response to the surgery. In addition, patients in the INCREASED group tended to develop more acute atrial fibrillation (35% vs. 14% incidence; p=0.112) than patients in the DECREASED group. Changes in plasma ANGPTL2 levels (ΔANGPTL2=final‐initial levels) positively correlated with the mRNA expression of the inflammatory markers TNF‐α and IL‐8 in both MAT and IMA at baseline (p&lt;0.05) and with the senescence‐associated marker p21 in IMA (p=0.009). In other words, high pre‐operative markers of inflammation and senescence were associated with an INCREASED in ANGPTL2 post‐operatively.ConclusionChanges in ANGPTL2 blood levels discriminate between two types of patients depending on known pre‐operative characteristics (age, blood pressure) and unknown inflammatory and senescent status. In younger patients with lower cardiac adipose tissue inflammation and arterial senescence load, ANGPTL2, but not hs‐CRP levels, decreased following cardiac surgery. A higher ANGPTL2 levels post‐cardiac surgery could potentially contribute to cardiovascular events such as atrial fibrillation. Altogether, our data suggest that circulating ANGPTL2 reflects tissue inflammation and senescence.Support or Funding InformationThis work was funded by grants from the Canadian Institutes of Health Research (MOP 133649 and 14496) (ET) and by the Foundation of the Montreal Heart Institute (ET, MC).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Reduction of plasma angiopoietin-like 2 after cardiac surgery is related to tissue inflammation and senescence status of patients

ObjectivesA strong relationship between high circulating angiopoietin-like 2 (ANGPTL2) levels, a proinflammatory adipokine, and cardiovascular diseases has been reported. Our objective was to determine whether plasma ANGPTL2 and high-sensitivity C-reactive protein (hs-CRP) levels change postoperatively in patients who underwent heart valve surgery and/or coronary artery bypass grafting. We hypothesized that a corrective cardiac surgery would decrease ANGPTL2 levels. MethodsIn 47 prospectively recruited patients who underwent coronary artery bypass grafting (n = 16), valve replacement (n = 16), or both (n = 15), we measured plasma ANGPTL2 and hs-CRP levels preoperatively, at 24 hours, at 3 to 5 days (hospital discharge), and at 30 to 90 days (follow-up) after surgery. Mediastinal adipose tissue and distal fragments of the left internal mammary artery (IMA) were harvested during surgery and mRNA expression of inflammatory and senescence markers was assessed using real-time quantitative polymerase chain reaction. ResultsANGPTL2 and hs-CRP levels were elevated 24 hours after surgery and then returned to baseline levels. We noted, however, a dichotomy among patients: compared with baseline, plasma ANGPTL2 levels either significantly decreased (n = 21/47) or increased (n = 26/47) after surgery. In contrast, hs-CRP levels were identical between groups (P = .997). Patients in the increased group were older (P = .002) with a higher systolic blood pressure (P = .038) at baseline. Moreover, changes in ANGPTL2 levels (ΔANGPTL2 = final minus initial levels) positively correlated with mRNA expression of tumor necrosis factor α and interleukin 8 in mediastinal adipose tissue and IMA (P < .05) and with the senescence-associated marker cyclin-dependent kinase inhibitor 1 in IMA (P = .009). ConclusionsIn younger patients with lower levels of tissue inflammation and arterial senescence load, ANGPTL2, but not hs-CRP levels decreased after cardiac surgery, suggesting that circulating ANGPTL2 reflects tissue inflammation and senescence.

Epicardial Fat Distribution Assessed with Cardiac CT in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

Purpose To compare epicardial fat in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) with that in healthy subjects. Materials and Methods In this retrospective study, cardiac CT scans in 44 patients with ARVD/C (mean age, 39 years ± 12; 23 men) were compared with those in 45 control group participants between January 2008 and July 2015. Volumes of intrathoracic adipose tissue, mediastinal adipose tissue (MAT), and total epicardial adipose tissue (EAT) were quantified. EAT was subdivided into three regions-right ventricular (RV) EAT, left ventricular (LV) EAT, and peri-atrial EAT (atrial EAT)-and normalized to MAT for all regions. Logistic regression and receiver operating characteristic analysis were performed to evaluate the association between epicardial fat with the diagnosis of ARVD/C. Results Total EAT volume was higher in patients with ARVD/C than in healthy control group participants (median, 98 mL vs 76 mL, respectively; P = .04). Regionally, LV and RV EAT volumes were higher in patients with ARVD/C than in control group participants, most notably when indexed to MAT (median LV EAT index: 0.49 vs 0.15, respectively; median RV EAT index: 0.91 vs 0.52; P ˂ .0005 for both). The optimal cutoff for diagnosis of ARVD/C was an LV EAT index of 0.24, with a sensitivity and specificity of 91% and 71%, respectively. Atrial EAT volume and total intrathoracic adipose tissue volume were not different between groups. RV diameter showed a positive correlation with total EAT index and LV EAT index (r = 0.21, P = .05 and r = 0.33, P = .002, respectively). Conclusion Higher amounts of right ventricular and left ventricular epicardial fat are found in hearts with arrhythmogenic right ventricular dysplasia/cardiomyopathy, particularly adjacent to the left ventricle, which correlates with disease severity and helps differentiate patients from healthy subjects. © RSNA, 2018 Online supplemental material is available for this article.

Immunohistochemical Evaluation of TLR-4 Response in the Mediastinal Adipose Tissue of Pigs Infected Naturally With Mycoplasma hyopneumoniae

Immunohistochemical Evaluation of TLR-4 Response in the Mediastinal Adipose Tissue of Pigs Infected Naturally With Mycoplasma hyopneumoniae

Role of Adipose Tissue Endothelial ADAM17 in Age-Related Coronary Microvascular Dysfunction.

A disintegrin and metalloproteinase ADAM17 (tumor necrosis factor-α [TNF]-converting enzyme) regulates soluble TNF levels. We tested the hypothesis that aging-induced activation in adipose tissue (AT)-expressed ADAM17 contributes to the development of remote coronary microvascular dysfunction in obesity. Coronary arterioles (CAs, ≈90 µm) from right atrial appendages and mediastinal AT were examined in patients (aged: 69±11 years, BMI: 30.2±5.6 kg/m2) who underwent open heart surgery. CA and AT were also studied in 6-month and 24-month lean and obese mice fed a normal or high-fat diet. We found that obesity elicited impaired endothelium-dependent CA dilations only in older patients and in aged high-fat diet mice. Transplantation of AT from aged obese, but not from young or aged, mice increased serum cytokine levels, including TNF, and impaired CA dilation in the young recipient mice. In patients and mice, obesity was accompanied by age-related activation of ADAM17, which was attributed to vascular endothelium-expressed ADAM17. Excess, ADAM17-shed TNF from AT arteries in older obese patients was sufficient to impair CA dilation in a bioassay in which the AT artery was serially connected to a CA. Moreover, we found that the increased activity of endothelial ADAM17 is mediated by a diminished inhibitory interaction with caveolin-1, owing to age-related decline in caveolin-1 expression in obese patients and mice or to genetic deletion of caveolin-1. The present study indicates that aging and obesity cooperatively reduce caveolin-1 expression and increase vascular endothelial ADAM17 activity and soluble TNF release in AT, which may contribute to the development of remote coronary microvascular dysfunction in older obese patients.

Cefazolin Concentration in the Mediastinal Adipose Tissue of Patients Undergoing Cardiac Surgery.

ObjectiveTo measure the concentration of cefazolin in the anterior mediastinal adipose tissue of patients undergoing cardiac surgery, determining the variation of cefazolin concentration.MethodsTwo samples of approximately 1g of subcutaneous tissue were collected from 19 patients who underwent surgery in December 2015: the first sample was collected right after sternotomy and the second one, before sternal synthesis with steel wires. Antibiotic dosage was administered through high performance liquid chromatography.ResultsWe observed a positive and statistically significant correlation between time 1 and cefazolin concentration (r=0.489 and P=0.039). For time 2 and cefazolin concentration, there was a negative and statistically significant correlation between both variables (r=-0.793 and P<0.001). A negative correlation was also observed between body mass index and cefazolin concentration at time 2 (r=-0.510 and P=0.031). The regression model showed that every 1-minute increase in time 1 corresponded to an increase of 0.240 µg/dL in cefazolin concentration, whereas every 1-minute increase in time 2 corresponded to a reduction of 0.046 µg/dL in cefazolin concentration. As for body mass index, every 1 kg/m2 increase corresponded to a reduction of about 0.510 µg/dL in cefazolin concentration.ConclusionThere was a positive and significant correlation between the initial time of surgery and cefazolin level in the first dosage. The evaluation of the second dosage showed a negative and significant correlation between cefazolin level and the second time of dosage. The concentration of cefazolin is under the influence of body mass index.

Frailty Syndrome: Visceral Adipose Tissue and Frailty in Patients with Symptomatic Severe Aortic Stenosis.

In patients with severe aortic stenosis (AS), frailty is a clinically relevant measure of increased vulnerability that should be included in the preoperative risk assessment. Bioelectrical impedance analysis (BIA) derived phase angle (PA) reflects cell membrane integrity and function. Few studies are available on the relative contribution of adiposity distribution on frailty, and about the influences of frailty and visceral obesity in PA value. Therefore, we aimed to evaluate associations among frailty, visceral fat depots and PA in patients with symptomatic severe AS. In a cohort of patients with symptomatic severe AS and preserved ejection fraction, we examined the associations between frailty, visceral fat depots and bioelectrical impedance analysis (BIA) derived phase angle (PA); and between visceral fat and PA. Frailty was defined according the Fried et al. scale criteria and the body fat distribution was determined by multidetector computed tomography and by BIA. Of the fifty-five included patients, 26 were frail (47%). Adjusting for age and gender, frailty was associated with indexed epicardial adipose tissue volume (EATVi) (the odds of frailty increased 4.1-fold per additional 100 cm3/m2 of EAT [95% confidence interval (CI) of 1.03 to 16.40, p=0.04] and with PA (OR of 0.50, 95% CI, 0.26 to 0.97, p=0.04), but not with body mass index (BMI), waist circumference (WC), indexed total, visceral and subcutaneous abdominal fat areas (TAFAi, VAFAi and SAFAi) nor with indexed mediastinal adipose tissue volume (MATVi). In an age and gender adjusted linear model, PA was inversely correlated with EATVi (β=-0.008, 95% CI, -0.016 to -0.001, p=0.03), but not with BMI, WC, nor with MATVi, VAFAi, SAFAi and TAFAi. In patients with symptomatic severe AS, EATVi is associated with frailty, independently of age and gender, but not with MAFVi or VAFAi. Moreover, frailty and EATVi are associated with impaired cell membrane integrity and function assessed by PA.

The role of adenovirus 36 induced obesity in obese adults with cardiovascular disorders: The first clinical study investigating ad-36 antibody in sera and DNA in mediastinal adipose tissues of cases with cardiovascular disorders from Turkey (A preliminary study)

The role of adenovirus 36 induced obesity in obese adults with cardiovascular disorders: The first clinical study investigating ad-36 antibody in sera and DNA in mediastinal adipose tissues of cases with cardiovascular disorders from Turkey (A preliminary study)

Effects of dietary trans-9 octadecenoic acid, trans-11 vaccenic acid and cis-9, trans-11 conjugated linoleic acid in mice.

The aim of the present study was to investigate the effects of dietary trans fatty acids in mice. Following the administration of a 0.5/100 g diet of trans-9 octadecenoic acid (EA), trans-11 vaccenic acid (TVA) or cis-9, trans-11 conjugated linoleic acid (CLA) for 4 weeks, the body weights and the weights of the liver, testis and mediastinal adipose tissue (MAT) of the animals gradually decreased (P<0.05). The EA group exhibited the lowest levels of magnesium and triglycerides (P<0.05). CLA increased villus length (P<0.05), while EA and TVA decreased villus length (P<0.05). The TVA group exhibited the lowest levels of low-density lipoprotein and tumor necrosis factor-α (P<0.05). Taken together, EA, TVA and CLA affected the physiological conditions of mice differently. The potential effects of three well-known fatty acids, including trans-9 octadecenoic acid (EA), trans-11 vaccenic acid (TVA) and cis-9, trans-11 conjugated linoleic acid (CLA), in animals or humans remain to be elucidated. Therefore, in the present study, 32 animals were randomly divided into four groups and administered a 0.5/100 g diet of EA, TVA or CLA for 4 weeks. The results demonstrated that the body weights and the weights of the liver, testis and mediastinal adipose tissue (MAT) of the animals gradually decreased (P<0.05). Blood was collected individually via the external jugular veins and the EA group exhibited the lowest levels of magnesium and triglycerides (P<0.05). CLA increased villus length (P<0.05), while EA and TVA decreased villus length (P<0.05). The TVA group exhibited the lowest levels of low-density lipoprotein and tumor necrosis factor-α (P<0.05). Taken together, EA, TVA and CLA affected the physiological conditions of mice differently and these may further our understanding of the various effects of these fatty acids on animals and humans.

A Case of Resected Plasma Cell Type Castleman’s Disease with Intramediastinal Lymph Nodes Spread

We report a case of resected plasma cell (PC) type Castleman's disease (CD) in a 21-year-old female who had an anterior mediastinal mass with additional surrounding nodules. She was aware of low-grade fever and fatigue for several years. From hematological and biochemical examinations, elevated inflammatory responses and levels of serum IgG (2908 mg/dL) and IL-6 (22.2 pg/mL) were observed. She was diagnosed with PC type CD by needle biopsy under computed tomography (CT) guidance. It was thought that the lesion was localized in the mediastinum. Then, mediastinal adipose tissue including the tumor, additional nodules and thymus were removed. The histological findings of PC type CD were found not only in the main tumor but also in surrounding swollen lymph nodes. Her symptoms improved and inflammatory responses decreased after the operation. No recurrence has been observed for 5 years after the operation.

Optimization of the isolation and expansion method of human mediastinal–adipose tissue derived mesenchymal stem cells with virally inactivated GMP-grade platelet lysate

Mesenchymal stem cells (MSCs) are adult multipotent cells currently employed in several clinical trials due to their immunomodulating, angiogenic and repairing features. The adipose tissue is certainly considered an eligible source of MSCs. Recently, putative adipose tissue derived MSCs (ADMSCs) have been isolated from the mediastinal depots. However, very little is known about the properties, the function and the potential of human mediastinal ADMSCs (hmADMSCs). However, the lack of standardized methodologies to culture ADMSCs prevents comparison across. Herein for the first time, we report a detailed step by step description to optimize the isolation and the expansion methodology of hmADMSCs using a virally inactivated good manufacturing practice (GMP)-grade platelet lysate, highlighting the critical aspects of the procedure and providing useful troubleshooting suggestions. Our approach offers a reproducible system which could provide standardization across laboratories. Moreover, our system is time and cost effective, and it can provide a reproducible source of adipose stem cells to enable future studies to unravel new insights regard this promising stem cell population.

Lack of adenovirus DNA in mediastinal adipose tissue of obese/overweight adults with cardiovascular disorders?

Mediastinal adipose tissue can be found on the anterior surface of pericardial sac below the remnants of the thymus. On the basis of previous studies describing adenoviruses (AdVs) as a causative factor of obesity, the causative relation between the presence of AdVs and an increased accumulation of mediastinal adipose tissue was studied. The study included 25 obese/overweight subjects with cardiac disorders. Specimens from fat deposits from the anterior mediastinum were collected during cardiac surgery procedures. Afterwards, PCR was used to detect AdV-DNA. No AdV-DNA could be detected in adipose tissue. An association between an excessive accumulation of mediastinal adipose tissue and an AdV-infection in the development of accompanying cardiac disorders was excluded.

Comparison of Epicardial Fat Volume by Computed Tomography in Black Versus White Patients With Acute Chest Pain

Disparities in the risk of coronary artery disease (CAD) between races may be influenced by differences in the thoracic adipose tissue. We compared computed tomography (CT)-derived volumes of epicardial adipose tissue (EAT), mediastinal adipose tissue (MAT), and pericoronary fat thickness (PFT) and correlations with CAD between black and white patients. This institutional review board-approved Health Insurance Portability and Accountability Act-compliant study included 372 age- and gender-matched black versus white patients (186 black, 54 ± 11 years, 50% men; 186 white, 54 ± 11 years, 50% men) who underwent CT for chest pain evaluation. EAT, MAT, and PFT were measured. The amount of coronary calcium was quantified as calcium score. CAD was defined as ≥50% coronary artery narrowing. EAT and MAT volumes were significantly lower in black than white patients (59 [twenty-fifth to seventy-fifth percentile 39 to 84] vs 97 [67 to 132] cm(3) and 44 [27 to 77] vs 87 [52 to 157] cm(3), for both p <0.001). Mean PFT in black patients was slightly lower than white patients (17.2 ± 3.2 vs 18.1 ± 3.4 mm, p <0.01). The relation between race and extent of adipose tissue remained significant after adjustment for cardiovascular risk factors. Significant correlations were observed between EAT and MAT volumes and calcium score in black and white patients (r = 0.19 to 0.26, p <0.01). For both races, the level of thoracic fat measurements was higher in present versus absent coronary calcification. A greater amount of thoracic fat was found with obstructive CAD only in white patients. In conclusion, CT-derived measurements of thoracic fat differ between symptomatic black and white patients, suggesting a differential relation between thoracic adipose tissue and CAD pathophysiology by race.

Ceramides are associated with inflammatory processes in human mediastinal adipose tissue

Background and AimCeramides are poorly characterized in human adipose tissue. The aim of this study was to investigate concentrations of different ceramide species in human subcutaneous and visceral adipose tissue depots and to determine associations between ceramides and global gene expression profiles. Methods and ResultsConcentrations of six ceramide species were determined in plasma and in subcutaneous and mediastinal adipose tissue from 10 overweight subjects (BMI 29.4 ± 4.9 kg/m2). In the adipose tissue biopsies gene expression arrays were performed and relationships between ceramides and gene expression analyzed. Immunostaining of the two adipose tissue depots was performed in an independent group of 10 patients. Mediastinal adipose tissue contained significantly higher concentrations (p < 0.05) of all six ceramide species than the subcutaneous depot. Of the six ceramides in plasma, concentrations of only two (Cer d18:1/18:0 and Cer d18:1/22:0) correlated significantly (p < 0.05) with the corresponding species in mediastinal adipose tissue, but there were no significant correlations between ceramides in plasma and subcutaneous adipose tissue. Multivariate analysis identified significant correlations between the total ceramide concentration and global gene expression within mediastinal, but not subcutaneous adipose tissue, according to cross-validation. Gene ontology analysis of genes related to ceramides in the mediastinal depot revealed that genes positively correlated with ceramides were associated mainly with immune and inflammatory categories, while genes negatively correlated with ceramides were associated mainly with lipid and carbohydrate metabolism. ConclusionsCeramides in human mediastinal adipose tissue may be involved in inflammation and lipid and carbohydrate metabolism.

Relationship between epicardial adipose tissue and subclinical coronary artery disease in patients with extra‐cardiac arterial disease

Epicardial adipose tissue (EAT) and mediastinal adipose tissue (MAT) are linked to coronary artery disease (CAD). The association between EAT, MAT, and severity of CAD in known extra-cardiac arterial disease was investigated. Sixty-five cardiac asymptomatic patients (mean age 65 ± 8 years, 69% male) with peripheral arterial disease, carotid stenosis, or aortic aneurysm underwent coronary computed tomography angiography. Patients were divided into non-significant (<50% stenosis, N = 35), single vessel (N = 15) and multi-vessel CAD (N = 15). EAT and MAT were quantified on computed tomography images using volumetric software. Subgroups did not significantly differ by age, gender, or cardiovascular risk factors. Median EAT was 99.5, 98.0, and 112.0 cm(3) (P = 0.38) and median MAT was 66.0, 90.0, and 81.0 cm(3) (P = 0.53) for non-significant, single vessel, and multi-vessel CAD, respectively. In age- and gender-adjusted analysis, only EAT was significantly associated with CAD (odds ratio [OR] 1.12 [95% confidence interval, 1.01-1.25] per 10 cm(3) increase in EAT; P = 0.04). This remained in multivariate-adjusted analysis (OR 1.21 [1.04-1.39]; P = 0.01). In patients with known extra-cardiac arterial disease, CAD is correlated with EAT, but not with MAT. These results suggest that EAT has a local effect on coronary atherosclerosis, apart from the endocrine effect of visceral fat.