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Expression profiles of epicardial and subcutaneous adipose tissue

ABSTRACT: The epicardial adipose tissue (EAT) is a visceral adipose tissue in close contact with coronary vessels whose increase is associated with coronary artery disease (CAD). Our goal was to identify candidate molecule(s) characterizing EAT which could intervene in the pathogenesis of CAD. An approach combining microarrays and bioinformatic sequence analysis tools for predicting secreted proteins (TargetP) was applied to paired biopsies of subcutaneous adipose tissue (SAT) and EAT, obtained from patients with or without CAD (NCAD). Results were validated in 3 independent groups of subjects by RT-qPCR, western blot, immuno histochemistry and explants secretion. sPLA2-IIA ranked first among genes coding for potentially secreted proteins with the highest overexpression in EAT in both CAD and NCAD. RT-qPCR confirmed its increased expression in EAT ( p<0.01) and in EAT from CAD as compared to NCAD (49.3 ±13 vs. 17.4 ± 9.7 p<0.01). sPLA2-IIA protein level was higher in EAT than in SAT. EAT explants demonstrated also significantly higher sPLA2-IIA secretion levels than SAT ones (4.37±2.7 vs 0.67± 0.28 ng.ml-1/g tissue/24h,p<0.03). sPLA2-IIA labeling was evidenced in EAT in the stroma vascular fraction between adipocytes and in connective capsules, with no immunostaining of the adipocytes. SAT was weakly labeled following the same pattern. Conclusion: We evidenced for the first time an increased expression of sPLA2-IIA in EAT from patients with CAD, a phospholipase that was shown to be an independent risk factor for CAD. These findings suggest a potentially pathophysiological role of EAT in CAD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE18612 | GEO | 2021/10/20

SECONDARY ACCESSION(S): PRJNA121441

REPOSITORIES: GEO

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Project description:Rationale: Epicardial adipose tissue (EAT) has been independently associated with non-calcified, high-risk coronary plaques in low-to intermediate risk subjects. Recently, a bidirectional communication was shown between EAT and diseased coronary arteries. In high-risk patients it is unknown whether quantitative measures of EAT can capture, and which molecular players are involved in this mutual interplay. Objective: In a high-risk population, we aimed to determine how the volume of EAT is linked to coronary artery disease (CAD) and to identify potential EAT-deregulated pathways in CAD patients specifically related to coronary artery calcification (CAC). Methods and Results: In a prospective cohort of 574 degenerative severe aortic stenosis patients referred to cardiac surgery, we quantified fat depots by computed tomography (CT) and performed a comparative quantitative proteomics of thoracic fat, including EAT, mediastinal (MAT) and subcutaneous (SAT) adipose tissues. We did not find an independent association of EAT volume with the severity, distribution and complexity of coronary stenosis in invasive coronary angiography. Although, EAT volume was correlated with high CAC, its cardiovascular risk factors-adjusted association was not significant. Taking as reference non-CAD matched-patients and compared to MAT and SAT, EAT proteomic signature of CAD was characterized by up-regulation of pro-calcifying annexins (Annexin A2, ANXA2), fatty acid binding transporters (FABP4) and inflammatory signaling proteins, and by down-regulation of fetuin-A and redox state regulatory enzymes. In EAT, ANXA2 regulation was positively correlated with CAC. EAT gene expression studies confirmed overexpression of ANXA2 and FABP4 in CAD, but no expression of FETUA was detected. Compared with non-CAD, fetuin-A circulating levels were higher in CAD, whereas no fetuin-A pericardial fluid differences were found. Conclusions: In this high-risk cohort, EAT presented an imbalance of pro-calcifying, pro-inflammatory and lipid transporters mediators. These local EAT-mediated regulatory mechanisms were not reflected by the CT volume of EAT alone.

Project description:The biological functions of epicardial adipose tissue (EAT) remain largely elusive. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). Objectives of this study were to identify genes that are up- or down-regulated among three adipose tissues (AT), namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases. Samples were collected from patients undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in all three AT depots of six men using the lllumina® HumanWG-6 v3.0 expression BeadChips. Twenty-two and 73 genes were up-regulated in EAT compared to mediastinal and subcutaneous AT, respectively. Ninety-four genes were down-regulated in EAT compared to subcutaneous adipose depot. However, none were significantly down-regulated in EAT compared to mediastinal fat. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (epicardial > mediastinal > subcutaneous). The results of ADORA1 and PTGDS were confirmed by qPCR in 25 biological replicates. Overall, the transcriptional profiles of EAT and MAT were similar compared to the subcutaneous compartment. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD. Samples of epicardial, mediastinal and subscutaneous adipose tissue were collected from the chest of 6 male patients undergoing coronary artery bypass grafting surgeries. The RNA was labeled and hybridized using a standard Illumina protocol (https://icom.illumina.com/Login?ReturnUrl=%2ficom%2fsoftware.ilmn%3fid%3d214&id=214). Three pairwise comparison among the three adipose tissue were made using significance analysis of microarrays.

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Expression profiles of epicardial and subcutaneous adipose tissue

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