Epicardial adipokines in obesity and coronary artery disease induce atherogenic changes in monocytes and endothelial cells.
OBJECTIVE
To investigate the hypothesis that release of adipokines by epicardial adipose tissue (EAT) is dysregulated in obesity and/or coronary artery disease (CAD), along with the previously documented expansion of the tissue, and that these molecules induce pathophysiological changes in human monocytes and coronary artery endothelial cells.


RESULTS
In white nondiabetic patients with CAD (n=62) or without CAD (control group) (n=32), subdivided by body mass index of <or=27 and >27, 13 cytokines were identified by protein array analysis as EAT products. Interleukin 6, interleukin 8, monocyte chemoattractant protein 1, plasminogen activator inhibitor 1, growth-related oncogene-alpha, and macrophage migration inhibitory factor were the most abundant. Adiponectin release was suppressed in patients with obesity and CAD, and regulated on activation T-cell and secreted (RANTES) was induced in patients with CAD. EAT-conditioned media induced migration of monocytic tryptophan hydroxylase 1 (THP-1) cells, an effect exacerbated in those with CAD. Moreover, conditioned media from patients with CAD and body mass index of >27 increased the adhesion of THP-1 cells to human coronary artery endothelial cells by 15.1% (P=0.002) and expression of intercellular adhesion molecule 1 by 2.8-fold (P=0.002). This effect was reversed by recombinant adiponectin.


CONCLUSIONS
EAT products are altered in both obesity and CAD and induce atherogenic changes in relevant target cells.
Karastergiou
Kalypso
K
Adipokines and Metabolism Research Group, Centre for Clinical Pharmacology, Division of Medicine, University College London, London, England.
Evans
Ian
I
Ogston
Nicola
N
Miheisi
Nazar
N
Nair
Devaki
D
Kaski
Juan-Carlos
JC
Jahangiri
Marjan
M
Mohamed-Ali
Vidya
V
D054392:Adipokines / Q000097:blood / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D018920:Coculture Techniques; D003324:Coronary Artery Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017077:Culture Media, Conditioned / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009924:Organ Culture Techniques; D019899:Paracrine Communication; D010496:Pericardium / Q000378:metabolism*; D040081:Protein Array Analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D054392:Adipokines; D017077:Culture Media, Conditioned; D019040:E-Selectin; D018836:Inflammation Mediators; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1