Epicardial Adipose Tissue Adiponectin Research Articles

Glucose and Inflammatory Cells Decrease Adiponectin in Epicardial Adipose Tissue Cells: Paracrine Consequences on Vascular Endothelium.

Epicardial adipose tissue (EAT) is a source of energy for heart that expresses the insulin-sensitizer, anti-inflammatory and anti-atherogenic protein, adiponectin. But, in coronary artery disease, adiponectin production declines. Our objective was to determine its regulation by glucose and inflammation in stromal cells from EAT and subcutaneous adipose tissue (SAT) and its paracrine effect on endothelial cells. Stromal cells of EAT and SAT were obtained from patients who underwent cardiac surgery. Adipogenesis was induced at 117, 200, or 295 mg/dl glucose, with or without macrophage-conditioned medium (MCM). Expression of adiponectin, GLUT-4 and the insulin receptor was analyzed by real-time PCR. The paracrine effect of stromal cells was determined in co-cultures with endothelial cells, by exposing them to high glucose and/or MCM, and, additionally, to leukocyte-conditioned medium from patients with myocardial infarction. The endothelial response was determined by analyzing vascular adhesion molecule expression. Our results showed a U-shaped dose-response curve of glucose on adiponectin in EAT, but not in SAT stromal cells. Conversely, MCM reduced the adipogenesis-induced adiponectin expression of EAT stromal cells. The presence of EAT stromal increased the inflammatory molecules of endothelial cells. This deleterious effect was emphasized in the presence of inflammatory cell-conditioned medium from patients with myocardial infarction. Thus, high glucose and inflammatory cells reduced adipogenesis-induced adiponectin expression of EAT stromal cells, which induced an inflammatory paracrine process in endothelial cells. This inflammatory effect was lower in presence of mature adipocytes, producers of adiponectin. These results contribute to understanding the role of EAT dysfunction on coronary atherosclerosis progression.

Adiponectin and p53 mRNA in epicardial and subcutaneous fat from heart failure patients

Heart failure (HF) is associated with a pro-inflammatory state in epicardial fat, but the involved mechanisms are not entirely clear. The aim of our study was to assess the relationship between p53 and adiponectin mRNA in epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) in patients with heart failure and its sympathetic regulation. Epicardial adipose tissue and SAT samples were obtained from 63 patients undergoing elective cardiac surgery. EAT and SAT explants culture from seven patients were stimulated with isoprenaline 0.1 or 1 uM for 6 h. p53 and adiponectin mRNA expression was measured in frozen biopsies or explants culture from both fat pads by real-time polymerase chain reaction (PCR). We observed that EAT expressed more p53 mRNA than SAT (1.73 ± 0.07 vs. 1.69 ± 0.04, P < 0.001) and its levels were higher in HF patients (1.75 ± 0.07 vs. 1.70 ± 0.04, P < 0.01 in EAT and 1.70 ± 0.04 vs. 1.67 ± 0.04, P < 0.05 in SAT). Moreover, p53 mRNA expression was negatively correlated with adiponectin in EAT. After analysing the p53 mRNA regulation by isoprenaline, we observed that only EAT p53 expression increased after adrenergic stimulation (1.63 ± 0.01 vs. 1.66 ± 0.02; P = 0.024). p53 mRNA expression levels, inversely correlated with adiponectin, increase in EAT of HF patients and can be regulated by sympathetic activation pathway. Our findings can help to explain the deleterious effect of sympathetic activation in HF.

Baseline epicardial adipose tissue adiponectin levels predict cardiovascular outcomes: A long-term follow-up study

ObjectiveEpicardial adipose tissue (EAT) produces a wide range of adipokines and has recently been linked to the physiopathology of cardiovascular (CV) and metabolic diseases. We aimed to study whether EAT and subcutaneous (SAT) adiponectin and leptin expression levels are associated with CV complications during long-term follow-up. Methods and resultsEAT and SAT samples were obtained during surgery – mainly CABG (n=77) – from 137 patients (mean age 69.9years, 31% women). Adiponectin and leptin mRNA levels were analyzed by RT-PCR. Plasma adiponectin levels were determined in a subsample of subjects (n=43). Thirty-four patients developed CV complications during 41 (SD 23) months of mean follow-up. Patients with CV events had lower EAT and SAT adiponectin levels at baseline (12.4 (3.0) vs. 15.7 (3.8) a.u., P=0.001; and 13.7 (2.6) vs. 15.7 (4.4) a.u., P=0.048, respectively). However, baseline EAT and SAT leptin levels and plasma adiponectin levels were not significantly different between patients with/without CV events during follow-up. Cox proportional hazards models adjusting for covariates in stages revealed that only baseline EAT adiponectin levels and heart failure could predict CV events. ConclusionsEAT adiponectin levels are strong predictors of CV prognosis in patients with CV diseases. EAT is likely to play a major role in the development of CV complications mainly through local effects.

Correlation between severity of coronary artery atherosclerosis and epicardial adipose tissue adiponectin expression in patients with coronary artery disease

Objective To investigate the correlation between epicardial adipose tissue adiponectin expression in patients with coronary artery disease (CAD) and severity of coronary artery atherosclerosis.Methods Choose 52 cases in coronary artery disease group and valvular disease group of 54,took peripheral venous blood and epicardial adipose tissue.paitents were devied into three groups according to Gensini' s score.Adiponectin was measured with the use of enzyme linked immunosorbent assay ( ELISA ),reverse transcription-polymerase chain reaction (RT-PCR) was used to analysis adiponectin mRNA,Western blotting method was used to detect adiponectin protein expression.Results Serum adiponectin were valvular disease group ( 14.1 ± 4.2) mg/L,coronary heart disease group ( 9.3 ± 4.5 ) mg/L ( P ＜ 0.01 ).serum adiponectin of the three groups were ( 10.9 ± 5.5 ) mg/L ( n =16 ),( 8.4 ± 4.2 ) mg/L ( n =20 ),(6.2 ± 5.3 ) mg/L( n =18 ) ( P ＜ 0.05 ) ; RT-PCR and Western blotting analysis of adiponectin levels in epicardial adipose tissue showed a downward trend with increased Gensini' s score.Conclusion Epicardial adipose tissue levels of adiponectin was dreased in patient with CAD,low Epicardial adipose tissue levels of adiponectinwas related to the severity of coronary artery atherosclerosis. Key words: Coronary artery disease; Adiponectin; Epicardial adipose tissue

Lower epicardial adipose tissue adiponectin in patients with metabolic syndrome

BackgroundAdiponectin is an anti-atherogenic insulin-sensitizer hormone whose plasma concentration is lower in patients with metabolic syndrome (MS). Visceral adiposity, including epicardial adipose tissue (EAT), is closely related to the development of MS and coronary artery disease (CAD). We sought to study whether EAT and subcutaneous adipose tissue (SAT) adiponectin mRNA levels are similar in patients with and without MS. MethodsEAT, SAT and blood samples were collected from patients undergoing elective cardiac surgery, for revascularization (n=19) or other procedures (n=27). Plasma adiponectin was measured using ELISA. mRNA was purified and adiponectin mRNA quantified by real time RT-PCR. ResultsMean (SD) age was 71.6 (9.6)years. Patients who met Adult Treatment Panel III MS criteria (n=29) presented lower plasma adiponectin concentrations (11.2 (7.4) vs. 19.6 (8.4)mg/l, P=0.004), lower EAT adiponectin mRNA (12.7 (3.0) vs. 15.1 (3.7)a.u., P=0.029) and similar SAT adiponectin mRNA levels (13.7 (4.2) vs. 15.6 (5.7)a.u., P=0.25) than those without MS. After adjusting for age, sex, CAD and heart failure, the association with MS remained statistically significant for plasma adiponectin (OR 0.862 (0.762–0.974)), was of borderline significance for EAT adiponectin mRNA (OR 0.796 (0.630–1.005)) and not significant for SAT adiponectin mRNA (OR 0.958 (0.818–1.122)). Patients in the lower quartiles of EAT adiponectin mRNA and plasma adiponectin presented a higher mean of components of the MS. ConclusionsSubjects with MS present lower EAT adiponectin mRNA levels than those without MS, whereas SAT adiponectin mRNA levels do not seem to differ between both groups. EAT might be the link between MS and its atherothrombotic cardiac complications.

Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease

BackgroundDisorders of endocrine substances in epicardial adipose tissue are known causes of coronary artery disease (CAD). Adiponectin is associated with cardiovascular disease. However, expression of adiponectin in epicardial adipose tissue and its function in CAD pathogenesis is unclear. This study investigates adiponectin expression in epicardial adipose tissue in CAD patients.MethodsVessels or adipose tissue samples collected from CAD patients and non-CAD controls were examined after immunochemical staining. Adiponectin, cytokines of interleukin-6 (IL-6) and necrosis factor-α (TNF-α) and toll-like receptor 4 (TLR4) expression level in adipose tissue were measured using real-time quantitative RT-PCR. Adiponectin concentrations in peripheral and coronary sinus vein plasma were measured with enzyme-linked immunosorbent assay. Peripheral vein plasma biochemistries were performed with routine laboratory techniques. Monocytes were collected from blood using lymphocyte separation medium. Expression level of cytokines and transcription factor NF-κB were measured to learn the effect of adiponectin on stearic acid-stimulated monocytes. Percentage of TLR4 positive monocytes was analyzed using flow cytometry.ResultsHistological examination revealed increased macrophage infiltration into epicardial adipose tissue of CAD patients. Decreased adiponectin displayed by real-time quantitative RT-PCR was associated with enhanced cytokines of IL-6 and TNF-α or TLR4 expression level in epicardial adipose tissue, suggesting decreased circulating adiponectin may be useful as a more sensitive predictor for coronary atherosclerosis than routine laboratory examinations. Adiponectin suppressed secretion of IL-6 and TNF-α in stimulated monocytes and TLR4 was expressed on cell surfaces.ConclusionsEndocrine disorders in epicardial adipose tissue are strongly linked to CAD, and adiponectin has a protective effect by inhibiting macrophage-mediated inflammation.

Diabetic and nondiabetic patients express similar adipose tissue adiponectin and leptin levels

Epicardial adipose tissue (EAT) is an interesting visceral fat pad with a particular location. EAT and subcutaneous adipose tissue (SAT) produce a wide range of adipokines. Some of them, including adiponectin and leptin, can influence the risk of development of diabetes and other associated metabolic and cardiovascular conditions. We sought to assess whether EAT and SAT adiponectin and leptin expression levels are different in diabetic patients with respect to nondiabetic subjects. We collected samples of EAT from 120 patients and samples of SAT from 88 of the same group of patients undergoing elective cardiac surgery for coronary artery bypass grafting (n=69) or other procedures (n=51). After RNA isolation, adiponectin and leptin expression levels were analyzed by real-time reverse transcriptase PCR. Plasma levels were determined in small subsamples of subjects. Baseline clinical and treatment data were obtained from medical records. A total of 45 diabetic and 75 nondiabetic subjects were included in the study. Mean (s.d.) age was 70.1 (7.8) years and there were 32% women. EAT and SAT adiponectin and leptin mRNA expression levels were similar in the diabetic and the nondiabetic groups (EAT adiponectin 14.4 (4.3) vs 14.6 (3.4) arbitrary units (a.u.), P=0.79; SAT adiponectin 15.6 (4.7) vs 15.1 (3.9), P=0.54; EAT leptin 9.3 (interquartile range 2.5) vs 9.5 (1.9) a.u., P=0.72; SAT leptin 9.9 (3.6) vs 10.0 (2.5) a.u., P=0.96). These findings persisted after stratification for sex and coronary artery disease. Logistic regression models including possible confounders and a combination of diabetes and impaired fasting glucose as a dependent variable led to similar results. Plasma adiponectin levels were lower in diabetic patients, whereas leptin levels showed a nonsignificant trend. Diabetic and nondiabetic subjects express similar EAT and SAT adiponectin and leptin levels. Counter-regulatory mechanisms of adiponectin and leptin expression in patients with established diabetes might partly account for these findings.

Epicardial Adipose Tissue Adiponectin Expression is Related to Intracoronary Adiponectin Levels

The role of adiponectin and epicardial adipose tissue in coronary artery disease (CAD) is a subject of debate. Whether plasma adiponectin concentration in the coronary circulation is locally modulated by the epicardial fat is still unexplored. We evaluated the hypothesis whether intracoronary plasma adiponectin levels are related to adiponectin expression in epicardial adipose tissue in vivo in patients with CAD and without CAD (non-CAD). We examined 12 patients with CAD who required CABG and 10 patients with non-CAD who underwent cardiac surgery for valve replacement. Plasma levels of adiponectin were measured in peripheral vein circulation and in left coronary artery (LCA) during coronary angiography. Epicardial adipose tissue biopsy for adiponectin protein extraction was performed during cardiac surgery in both CAD and non-CAD subjects. Adiponectin protein expression in epicardial adipose tissue was lower in patients with CAD than in those with non-CAD (0.45+/-0.4 vs. 1.1+/-1.0, p<0.05). LCA plasma adiponectin levels significantly correlated with epicardial adipose tissue adiponectin protein expression (r=0.68, p=0.02) in all subjects. Peripheral adiponectin levels and epicardial fat adiponectin protein expression were the best correlates of LCA adiponectin, r (2)=0.49, p<0.01, p<0.05, respectively). Our study showed that intracoronary adiponectin levels reflect systemic adiponectin levels. Epicardial adipose tissue could partially contribute to adiponectin levels in the coronary circulation.

Extension of coronary artery disease is associated with increased IL-6 and decreased adiponectin gene expression in epicardial adipose tissue

Epicardial adipose tissue (EAT) expresses lower levels of adiponectin in patients with CAD and higher levels of inflammatory mediators such as IL-6 and leptin than subcutaneous adipose tissue. This showed one important role of EAT in coronary artery disease. However, the relationship of EAT adiponectin and IL-6 levels to the extension of coronary artery disease has not hitherto been determined. We sought to determine whether the levels of adiponectin and interleukin-6 (IL-6) mRNA in epicardial adipose tissue are associated with the extension of coronary artery disease (CAD). Methods: Angiographic and hormones expression were evaluated from epicardial and subcutaneous adipose tissue. 92 patients (58 CAD, 34 non-CAD) who underwent cardiac surgery. Adiponectin and IL-6 mRNA levels were measured by real time RT-PCR in epicardial and subcutaneous adipose tissue (SAT) following angiographic evaluation of their coronary arteries. Results: We found that epicardial adipose tissue of CAD expressed lower levels of adiponectin mRNA and higher levels of IL-6 mRNA than that of non-CAD patients. As the number of injured arteries rose, adiponectin mRNA levels decreased (r=−0.402, p<0.001) and IL-6 mRNA increased (r=0.514, p<0.001) in epicardial adipose tissue. Conclusions: The extension of CAD is significantly associated with the expression of adiponectin and IL-6 mRNA in EAT. These findings suggest that low adiponectin and high IL-6 expression by EAT may contribute to CAD extension.