The role of mediastinal adipose tissue 11β-hydroxysteroid d ehydrogenase type 1 and glucocorticoid expression in the development of coronary atherosclerosis in obese patients with ischemic heart disease

Abstract

Background: Visceral fat deposition and its associated atherogenic complications are mediated by glucocorticoids. Cardiac visceral fat comprises mediastinal adipose tissue (MAT) and epicardial adipose tissue (EAT), and MAT is a potential biomarker of risk for obese patients.

Aim: Our objective was to evaluate the role of EAT and MAT 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and glucocorticoid receptor (GCR) expression in comparison with subcutaneous adipose tissue (SAT) in the development of coronary atherosclerosis in obese patients with coronary artery disease (CAD), and to assess their correlations with CD68 and fatty acids from these tissues.

Methods and results: Expression of 11β-HSD-1 and GCR was measured by qRT-PCR in EAT, MAT and SAT of thirty-one obese patients undergoing coronary artery bypass grafting due to CAD (obese CAD group) and sixteen obese patients without CAD undergoing heart valve surgery (controls). 11β-HSD-1 and GCR expression in MAT were found to be significantly increased in the obese CAD group compared with controls (p < 0.05). In the obese CAD group, 11β-HSD-1 and GCR mRNA levels were strongly correlated in MAT. Stearidonic acid was significantly increased in EAT and MAT of the obese CAD group and arachidonic acid was significantly expressed in MAT of the obese male CAD group (p < 0.05).

Conclusions: We report for the first time the increased expression of 11β-HSD-1 and GCR in MAT compared with EAT and SAT, and also describe the interrelated effects of stearidonic acid, HOMA-IR, plasma cortisol and GCR mRNA levels, explaining 40.2% of the variance in 11β-HSD-1 mRNA levels in MAT of obese CAD patients. These findings support the hypothesis that MAT contributes locally to the development of coronary atherosclerosis via glucocorticoid action.

Figure 1

The mRNA expression of 11β-HSD1 and GCR in the study groups. A: The mRNA expression of 11β-HSD1 and GCR in 31 obese patients with CAD (obese CAD group) and 16 obese patients without CAD (control group) in epicardial adipose tissue (EAT), mediastinal adipose tissue (MAT) and subcutaneous adipose tissue (SAT). *p < 0.05, **p < 0.001 (Obese CAD group vs.control group). Data are mean ± SD. B: The mRNA expression of 11β-HSD1 and GCR in 16 females and 15 males obese patients with CAD in epicardial adipose tissue (EAT), mediastinal adipose tissue (MAT) and subcutaneous adipose tissue (SAT). * p < 0.05, **p < 0.001 (women vs.men). Data are mean ± SD, C: The mRNA expression of CD68 in 31 obese patients with CAD (obese CAD group) and 16 obese patients without CAD (control group) in epicardial adipose tissue (EAT), mediastinal adipose tissue (MAT) and subcutaneous adipose tissue (SAT). **p < 0.01 (Obese CAD group vs.control group). Abbreviations: A.U., Arbitrary Units.

Figure 2

Immunohistochemistry using human anti-CD68 for macrophages for epicardial, mediastinal and subcutaneous adipose tissues of obese CAD and control groups. CD68+ cells (macrophages) are observed in the epicardial, mediastinal and subcutaneous adipose tissues of obese CAD group (A, B and C) and control group (D, E and F). CD68+ cells (upwards arrow) between normal and large adipocytes (black asterisks) are identified in the adipose tissues. These findings were endorsed by qRT-PCR of CD68 mRNA expression in all three adipose tissues of the study group. Magnification: x 40 for A, B, C, D, E and F.

Figure 3

Scatter plot of 11β-HSD1 versus GCR in mediastinal adipose tissue (MAT) of obese CAD group. Correlation between mRNA levels of 11β-HSD1 and GCR were assessed using Spearman’s correlation.

Figure 4

The mRNA expression of Mineralocorticoid Receptor (MR) and TNF-α, IL-6 and adiponectin in 31 obese patients with CAD (obese CAD group) and 16 obese patients without CAD (control group) in epicardial adipose tissue (EAT), mediastinal adipose tissue (MAT) and subcutaneous adipose tissue (SAT). *p < 0.05, **p < 0.001 (Obese CAD group vs.controls). Data are mean ± SD.