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

Guauque-Olarte, Sandra; Gaudreault, Nathalie; Piché, Marie-Ève; Fournier, Dominique; Mauriège, Pascale; Mathieu, Patrick; Bossé, Yohan

doi:10.1371/journal.pone.0019908

Cited by 42 publications

(46 citation statements)

References 65 publications

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“…Interestingly, in EAT and MAT, controls showed significantly lower levels of stearidonic acid compared to obese patients with CAD, moreover arachidonic acid levels were significantly higher in male compared with female obese CAD patients in MAT. Interestingly, the significant expression of genes related with the arachidonic pathway in EAT was recently reported in a whole-genome gene expression microarray analysis of the EAT, MAT and SAT of six male patients suffering from CAD [44]. Our results confirm the expression of arachidonic acid in EAT and show for the first time its significant expression in MAT of obese male CAD patients.…”

Section: Discussionsupporting

confidence: 86%

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

Atalar

Görmez

Çaynak

et al. 2012

Cardiovasc Diabetol

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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.

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Section: Discussionsupporting

confidence: 86%

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

Atalar

Görmez

Çaynak

et al. 2012

Cardiovasc Diabetol

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“…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].…”

Section: Physiological Roles Of the Cardiac And Vascular Adipose Depotsmentioning

confidence: 90%

“…This creates a hypoxic microenvironment leading to diminished mitochondrial function, adrenergic signalling, increased inflammation and insulin resistance [61], [62], [63]. Data from rodents [43], sheep [64], [65] and humans [11] indicate that the cardiac and vascular adipose tissues are phenotypically brown during the early stages of life and despite whitening with age retain brown characteristics in adulthood [11], [21], [33]. It could be hypothesised that further whitening of cardiac and vascular adipose tissues in obesity and the subsequent dysfunction that occurs could drive a hypoxic, inflammatory microenvironment affecting the vasculature and driving coronary atherosclerosis (Fig.…”

Section: Cardiac and Vascular Adipose Tissue Dysfunctionmentioning

confidence: 99%

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

Aldiss

Davies

Woods

et al. 2017

International Journal of Cardiology

122

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Excess visceral adiposity, in particular that located adjacent to the heart and coronary arteries is associated with increased cardiovascular risk. In the pathophysiological state, dysfunctional adipose tissue secretes an array of factors modulating vascular function and driving atherogenesis. Conversely, brown and beige adipose tissues utilise glucose and lipids to generate heat and are associated with improved cardiometabolic health. The cardiac and thoracic perivascular adipose tissues are now understood to be composed of brown adipose tissue in the healthy state and undergo a brown-to-white transition i.e. during obesity which may be a driving factor of cardiovascular disease. In this review we discuss the risks of excess cardiac and vascular adiposity and potential mechanisms by which restoring the brown phenotype i.e. “re-browning” could potentially be achieved in clinically relevant populations.

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“…Upregulation of Pamr1 has also been associated with coronary artery disease (CAD) in epicardial and subcutaneous adipose tissue (53). Thus, one could hypothesize that inflammatory Table 1.…”

Section: Pamr1: An Er-stress-induced Protein Involved In Muscle Regenmentioning

confidence: 99%

An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes

et al. 2015

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Genome-wide association studies in human type 2 diabetes (T2D) have renewed interest in the pancreatic islet as a contributor to T2D risk. Chronic low-grade inflammation resulting from obesity is a risk factor for T2D and a possible trigger of β-cell failure. In this study, microarray data were collected from mouse islets after overnight treatment with cytokines at concentrations consistent with the chronic low-grade inflammation in T2D. Genes with a cytokine-induced change of >2-fold were then examined for associations between single nucleotide polymorphisms and the acute insulin response to glucose (AIRg) using data from the Genetics Underlying Diabetes in Hispanics (GUARDIAN) Consortium. Significant evidence of association was found between AIRg and single nucleotide polymorphisms in Arap3 (5q31.3), F13a1 (6p25.3), Klhl6 (3q27.1), Nid1 (1q42.3), Pamr1 (11p13), Ripk2 (8q21.3), and Steap4 (7q21.12). To assess the potential relevance to islet function, mouse islets were exposed to conditions modeling low-grade inflammation, mitochondrial stress, endoplasmic reticulum (ER) stress, glucotoxicity, and lipotoxicity. RT-PCR revealed that one or more forms of stress significantly altered expression levels of all genes except Arap3. Thapsigargin-induced ER stress up-regulated both Pamr1 and Klhl6. Three genes confirmed microarray predictions of significant cytokine sensitivity: F13a1 was down-regulated 3.3-fold by cytokines, Ripk2 was up-regulated 1.5- to 3-fold by all stressors, and Steap4 was profoundly cytokine sensitive (167-fold up-regulation). Three genes were thus closely associated with low-grade inflammation in murine islets and also with a marker for islet function (AIRg) in a diabetes-prone human population. This islet-targeted genome-wide association scan identified several previously unrecognized candidate genes related to islet dysfunction during the development of T2D.

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

Cited by 42 publications

References 65 publications

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

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

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

An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes

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