Epicardial Adipose Tissue as a Source of Nuclear Factor-B and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease
A. R. Baker,
A. L. Harte,
N. Howell,
D. C. Pritlove,
A. M. Ranasinghe,
N. F. da Silva,
E. M. Youssef,
K. Khunti,
M. J. Davies,
R. S. Bonser,
S. Kumar,
D. Pagano and
P. G. McTernan
Unit for Diabetes and Metabolism (A.R.B., A.L.H., D.C.P., N.F.d.S., E.M.Y., S.K., P.G.M.), University of Warwick, Warwick Medical School, Clinical Sciences Research Institute, UHCW, Coventry CV2 2DX, United Kingdom; Department of Cardiothoracic Surgery (N.H., A.M.R., R.S.B., D.P.), University of Birmingham, Birmingham B15 2TH, United Kingdom; Department of Health Sciences (K.K.), University of Leicester, Leicester General Hospital, and Department of Cardiovascular Sciences (M.J.D.), University of Leicester, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom
Address all correspondence and requests for reprints to: Dr. P. G. McTernan, Unit for Diabetes and Metabolism, University of Warwick, Warwick Medical School, Clinical Sciences Research Institute, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, United Kingdom. E-mail: p.g.mcternan{at}warwick.ac.uk.
Context: Visceral adipose tissue (AT) is known to confer a significantlyhigher risk of type 2 diabetes and cardiovascular disease. EpicardialAT has been shown to be related to cardiovascular disease andmyocardial function through unidentified mechanisms. EpicardialAT expresses an inflammatory profile of proteins; however, themechanisms responsible are yet to be elucidated.
Objectives: The objectives of the study were to: 1) examinekey mediators of the nuclear factor-B (NFB) and c-Jun N-terminalkinase (JNK) pathways in paired epicardial and gluteofemoral(thigh) AT from coronary artery disease (CAD) and control patientsand 2) investigate circulating endotoxin levels in CAD and controlsubjects.
Design: Serums and AT biopsies (epicardial and thigh) were obtainedfrom CAD (n = 16) and non-CAD (n = 18) patients. Inflammationwas assessed in tissue and serum samples through Western blot,real-time PCR, ELISAs, and activity studies.
Results: Western blotting showed epicardial AT had significantlyhigher NFB, inhibitory-B kinase (IKK)-, IKKβ, and JNK-1and -2 compared with thigh AT. Epicardial mRNA data showed strongcorrelations between CD-68 and toll-like receptor-2, toll-likereceptor-4, and TNF-. Circulating endotoxin was elevated inpatients with CAD compared with matched controls [CAD: 6.80± 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 ±0.57 EU/ml; P<0.05].
Conclusion: Epicardial AT from patients with CAD shows increasedNFB, IKKβ, and JNK expression compared with both CAD thighAT and non-CAD epicardial AT, suggesting a depot-specific aswell as a disease-linked response to inflammation. These studiesimplicate both NFB and JNK pathways in the inflammatory profileof epicardial AT and highlight the role of the macrophage inthe inflammation within this tissue.
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A. Dutour, V. Achard, H. Sell, N. Naour, F. Collart, B. Gaborit, A. Silaghi, J. Eckel, M.-C. Alessi, C. Henegar, et al. Secretory Type II Phospholipase A2 Is Produced and Secreted by Epicardial Adipose Tissue and Overexpressed in Patients with Coronary Artery Disease
J. Clin. Endocrinol. Metab.,
February 1, 2010;
95(2):
963 - 967.
[Abstract][Full Text][PDF]
B and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease
B (NF
, IKKβ, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-
. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 ± 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 ± 0.57 EU/ml; P<0.05]. 
