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

BackgroundVisceral 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.AimOur 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 resultsExpression 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).ConclusionsWe 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.

Relationship between epicardial adipose tissue thickness and early impairment of left ventricular systolic function in patients with preserved ejection fraction

“…Since sex differences have been demonstrated in associations between EAT and coronary artery atherosclerosis [20], the relationship between EAT thickness and early impairment of LV systolic function should also be clarified in male patients in comparison with the female population examined in the present study. Pericardial adipose tissue (also known as mediastinal adipose tissue), as another form of cardiac adipose tissue [4,25], represents another candidate for investigation, since it has been shown to contribute more to the development of cardiovascular diseases than EAT [26]. …”

Accumulation of epicardial fat rather than visceral fat is an independent risk factor for left ventricular diastolic dysfunction in patients undergoing peritoneal dialysis

“…Besides of macrophage accumulation, macrophage phenotypic change in epicardial adipose tissue of CAD patients is also demonstrated [35]. Moreover, as we look into the role of visceral fat in the pathogenesis of CAD, there is evidence which suggests that not only EpF but mediastinal adipose tissue contributes locally to the development of coronary atherosclerosis via glucocorticoid action [36]. Increased epicardial fat thickness is shown to be an independent risk factor for CAD in specific patients [37], and there are probably gender disparities in the association between epicardial adipose tissue volume and CAD [38].…”

‘Browning’ the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk

“…Its gene expression profile is closer to that of BAT than subcutaneous adipose tissue [11] and its transcriptome is also similar to EAT [21] in men with CVD. Paracardial adipose tissue expresses a pathogenic profile characterised by increased expression of glucocorticoids and macrophage infiltration during CAD [22], [23]. Hypothetically, it may be both thermogenic and a metabolically active endocrine organ capable of contributing to systemic inflammatory processes modulating CVD progression.…”