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Epicardial Adipose Tissue as a Source of Nuclear Factor-B and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease

By A. R. Baker, A. L. Harte, N. Howell, D. C. Pritlove, A. M. Ranasinghe, N. F. da Silva, E. M. Youssef, K. Khunti, Melanie J. Davies, R. S. Bonser, S. Kumar, D. Pagano and P. G. McTernan

Abstract

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. \ud \ud Objectives: The objectives of the study were to: 1) examine key mediators of the nuclear factor-B (NFB) 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. \ud \ud 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. \ud \ud Results: Western blotting showed epicardial AT had significantly higher NFB, inhibitory-B kinase (IKK)-, 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]. \ud \ud Conclusion: Epicardial AT from patients with CAD shows increased NFB, IKKβ, 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 NFB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue

Publisher: Endocrine Society
Year: 2009
DOI identifier: 10.1210/jc.2007-2579
OAI identifier: oai:lra.le.ac.uk:2381/8581
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  1. (2009). 94:261-267 originally published online Nov 4,
  2. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. doi
  3. (2002). Akira S doi
  4. (1998). An ancient system of host defense. doi
  5. Barnett AH,EggoMC,KumarS2002 Insulin and rosiglitazone regulationof lipolysis and lipogenesis in human adipose tissue in vitro. doi
  6. (2002). Barnett AH,Kumar S doi
  7. BarnettAH,McTernanCL,Kumar S2002Differences inadiponectinprotein expression: effectof fatdepots and type2diabetic status. Horm Metab Res 34:650–654 doi
  8. BorggrefeM,PapavassiliuT2007Volumetric assessmentof epicardial adipose tissuewith cardiovascularmagnetic resonance imaging.Obesity (Silver doi
  9. CornellRP1985Endogenous gut-derivedbacterial endotoxin tonically primes pancreatic secretion of insulin in normal rats. doi
  10. (2003). Epicardial fat from echocardiography: a new method for visceral adipose tissue prediction. doi
  11. (2000). Female mice heterozygous for IKKgamma/NEMOdeficiencies develop adermatopathy similar to the human X-linked disorder incontinentia pigmenti. doi
  12. FogelstrandL,Hulthe J,HultenLM,WiklundO,FagerbergB2004Monocytic expression of CD14 and CD18, circulating adhesion molecules and inflammatory markers in women with diabetes mellitus and impaired glucose tolerance. doi
  13. (2000). Hannekum A doi
  14. (2003). Human epicardial adipose tissue is a source of inflammatory mediators.
  15. (2005). IKK- links inflammation to obesityinduced insulin resistance. doi
  16. (2005). Imaging of visceral adipose tissue: an emerging diagnostic tool and therapeutic target. Curr Drug Targets Cardiovasc Haematol Disord 5:345–353 doi
  17. (2006). Increased intestinal permeability in obese mice: new evidences in the pathogenesis of nonalcoholic steatohepatitis.
  18. (2006). Inflammation and insulin resistance.
  19. (2004). Inhibitor B kinase is involved in the paracrine crosstalk between human fat and muscle cells. doi
  20. Kumar S,McTernanPG2006Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease.
  21. (2004). Leptin and hyperleptinemia–from friend to foe for cardiovascular function. doi
  22. (2007). Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. doi
  23. (2007). McTernan PG
  24. (2001). Pathophysiological role of cytokines in congestive heart failure. Annu Rev Med 52:15–27 doi
  25. (2001). Remacle J
  26. (2003). Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. doi
  27. (1999). The role of TNF in cardiovascular disease. doi
  28. (2000). Toll-like receptor family and signallingpathway.BiochemSocTrans28:563–566 doi

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