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. METHODS AND 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.
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. METHODS AND RESULTS: In white nondiabeticpatients 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.
Authors: Nikki A Ford; Kaylyn L Devlin; Laura M Lashinger; Stephen D Hursting Journal: J Mammary Gland Biol Neoplasia Date: 2013-10-04 Impact factor: 2.673