Abstract

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Recent studies suggest that pericardial adipose tissue (PCAT) secretes inflammatory factors that contribute to the development of CVD. To better characterize the role of PCAT in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between PCAT and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals. As it was unknown whether PCAT-secreted factors are produced by adipocytes or cells in the supporting stromal fraction, we also sought to identify differentially expressed genes in isolated pericardial adipocytes vs. isolated subcutaneous adipocytes. Using microarray analysis, we found that: 1) pericardial adipose tissue and isolated pericardial adipocytes both overexpress atherosclerosis-promoting chemokines and 2) pericardial and subcutaneous fat depots, as well as isolated pericardial adipocytes and subcutaneous adipocytes, express specific patterns of homeobox genes. In contrast, a core set of lipid processing genes showed no significant overlap with differentially expressed transcripts. These depot-specific homeobox signatures and transcriptional profiles strongly suggest different functional roles for the pericardial and subcutaneous adipose depots. Further characterization of these inter-depot differences should be a research priority.

Highlights

  • Cardiovascular disease (CVD) has long been the leading cause of death in the U.S and the developed world [1]

  • We further found that pericardial adipose tissue (PCAT) and pericardial adipocytes (pcAds) both overexpress atherosclerosispromoting chemokines

  • RNA samples were isolated from SQAT, PCAT, sqAds, and pcAds, of which 53 samples (11 SQAT, 11 PCAT, sqAds, and pcAds) passed quality standards for hybridization to Affymetrix U133A Plus 2.0 microarrays

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Summary

Introduction

Cardiovascular disease (CVD) has long been the leading cause of death in the U.S and the developed world [1]. In part because of the strong correlation between the size of the visceral adipose tissue (VAT) depot and the incidence of CVD, type 2 diabetes mellitus, and metabolic syndrome, attention has focused on understanding the molecular and functional differences between VAT and subcutaneous adipose tissue (SQAT) [7][8][9]. With regards to CVD, IL-6 has been interesting because of its close association to inflammation, obesity, and coronary heart disease [13]. It is a strong, independent marker for increased mortality in the setting of CAD [14]

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