What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Coronary Artery Disease (n=31). Intervention: Epicardial adipose tissue (EAT) gene expression profiling vs. Mediastinal (MAT) and Subcutaneous (SAT) adipose tissues. Primary outcome: Differentially expressed genes among EAT, MAT, and SAT.

May 16, 2011Open Access

The Transcriptome of Human Epicardial, Mediastinal and Subcutaneous Adipose Tissues in Men with Coronary Artery Disease

Key Result

In men with coronary artery disease, the genes ADORA1 and PTGDS were significantly up-regulated in epicardial adipose tissue compared to mediastinal and subcutaneous adipose tissues.

Study Design

Type

Cross-Sectional (n=31)

Multicenter

Structured PICO

Population

31 predominantly overweight white men with coronary artery disease (1 to 3 affected vessels) undergoing coronary artery bypass grafting (CABG). The cohort included a microarray group (n=6) and a qPCR validation group (n=25).

Outcome

Differentially regulated genes among epicardial (EAT), mediastinal (MAT), and subcutaneous (SAT) adipose tissuessurrogate

Epicardial adipose tissue exhibits a distinct transcriptomic profile compared to subcutaneous fat, highlighted by the up-regulation of ADORA1 and PTGDS, suggesting a potential local role in the pathogenesis of coronary artery disease.

Limitations

Limited to subjects with CAD, cannot be extrapolated to non-CAD subjects.
Measured mRNA expression only, without quantification of protein levels.
Small sample size used in the microarray experiment.
Did not take into account the various cell types which composed the different fat depots.

Abstract

BACKGROUND: The biological functions of epicardial adipose tissue (EAT) remain largely unknown. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). The objectives of this study were to identify genes differentially regulated among three adipose tissues, namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases. METHODS AND RESULTS: Samples were collected from subjects undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in the three adipose depots of six men using the Illumina® HumanWG-6 v3.0 expression BeadChips. Twenty-three and 73 genes were differentially up-regulated in EAT compared to MAT and SAT, respectively. Ninety-four genes were down-regulated in EAT compared to SAT. However, none were significantly down-regulated in EAT compared to MAT. 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 (EAT>MAT>SAT). The results of ADORA1 and PTGDS were confirmed by quantitative real-time PCR in 25 independent subjects. CONCLUSIONS: Overall, the transcriptional profiles of EAT and MAT were similar compared to the SAT. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD.

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