Epicardial adipose tissue as a source of nuclear factor-kappa B and c-Jun N-terminal kinase mediated inflammation in patients with coronary artery disease
Baker, Adam R., Harte, A. L. (Alison L.), Howell, N., Pritlove, D. C., Ranasinghe, A. M., da Silva, N. F., Youssef, E. M., Khunti, Kamlesh, Davies, M. J., Bonser, R. S., Kumar, Sudhesh, Pagano, D. and McTernan, P. G. (Philip G.). (2009) Epicardial adipose tissue as a source of nuclear factor-kappa B and c-Jun N-terminal kinase mediated inflammation in patients with coronary artery disease. Journal of Clinical Endocrinology & Metabolism , Vol.94 (No.1). pp. 261-267. ISSN 0021-972xFull text not available from this repository.
Official URL: http://dx.doi.org/10.1210/jc.2007-2579
Context: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated.
Objectives: The objectives of the study were to: 1) examine key mediators of the nuclear factor-kappa B (NF kappa B) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects.
Design: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies.
Results: Western blotting showed epicardial AT had significantly higher NF kappa B, inhibitory-kappa B kinase (IKK)-gamma, IKK beta, 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-alpha. 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].
Conclusion: Epicardial AT from patients with CAD shows increased NF kappa B, IKK beta, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NF kappa B and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue. (J Clin Endocrinol Metab 94: 261-267, 2009)
|Item Type:||Journal Article|
|Subjects:||R Medicine > RC Internal medicine|
|Divisions:||Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI)
Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health
Faculty of Medicine > Warwick Medical School
|Journal or Publication Title:||Journal of Clinical Endocrinology & Metabolism|
|Official Date:||January 2009|
|Number of Pages:||7|
|Page Range:||pp. 261-267|
|Access rights to Published version:||Open Access|
|Funder:||Dunhill Medical Trust, British Medical Association (BMA), Overweight and Heart Disease Research Trust, Arden Medical Research Fund, British Medical Association: Lansdell and Lawson, British Heart Foundation|
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