Epicardial Adipose Tissue as a Source of Nuclear Factor-κB and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease
Epicardial Adipose Tissue as a Source of Nuclear Factor-κB and c-Jun N-Terminal Kinase Mediated Inflammation in Patients with Coronary Artery Disease
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DOI：
10.1210/jc.2007-2579
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发表时间：
2009-01-01
影响因子：
5.8
通讯作者：
McTernan, P. G.
中科院分区：
文献类型：
--
作者：
Baker, A. R.;Harte, A. L.;McTernan, P. G.
背景：众所周知，内脏脂肪组织（AT）可显著增加2型糖尿病和心血管疾病的风险。心外膜AT已被证明与心血管疾病和心肌功能有关，但机制尚未明确。心外膜AT表达炎性蛋白谱；然而，其机制还有待阐明。目的：本研究的目的是：1)检测冠状动脉疾病（CAD）和对照患者配对心外膜和股肌（大腿）AT中核因子- κ B （NF κ B）和c-Jun n末端激酶（JNK）通路的关键介质；2)调查CAD和对照患者循环内毒素水平。设计：从CAD （n = 16）和非CAD （n = 18）患者中获得血清和AT活检（心外膜和大腿）。通过Western blot， real-time PCR， elisa和活性研究评估组织和血清样本中的炎症。结果：Western blot结果显示，与大腿AT相比，心外膜AT的NF κ B、抑郁性κ B激酶(IKK)- γ、IKK β、JNK-1和-2明显升高。心外膜mRNA数据显示CD-68与toll样受体-2、toll样受体-4和tnf - α之间有很强的相关性。与对照组相比，冠心病患者循环内毒素升高[CAD: 6.80 +/- 0.28内毒素单位(EU)/ml，对照组：5.52 +/- 0.57 EU/ml；P < 0.05]。结论：与CAD大腿AT和非CAD心外膜AT相比，CAD患者的心外膜AT显示NF kappa B、IKK β和JNK表达增加，表明这是一种特异性的疾病反应，也是一种与炎症相关的疾病反应。这些研究暗示了NF κ B和JNK通路在心外膜AT炎症谱中的作用，并强调了巨噬细胞在该组织炎症中的作用。[J] .中华内分泌杂志，2009,31(3):391 - 397。
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)