Baker A R, Harte A L, Howell N, Pritlove D C, Ranasinghe A M, da Silva N F, Youssef E M, Khunti K, Davies M J, Bonser R S, Kumar S, Pagano D, McTernan P G
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.
J Clin Endocrinol Metab. 2009 Jan;94(1):261-7. doi: 10.1210/jc.2007-2579. Epub 2008 Nov 4.
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.
The objectives of the study were to: 1) examine key mediators of the nuclear factor-kappaB (NFkappaB) 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.
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.
Western blotting showed epicardial AT had significantly higher NFkappaB, inhibitory-kappaB kinase (IKK)-gamma, IKKbeta, 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].
Epicardial AT from patients with CAD shows increased NFkappaB, IKKbeta, 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 NFkappaB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.
已知内脏脂肪组织（AT）会显著增加患2型糖尿病和心血管疾病的风险。已表明心外膜脂肪组织通过不明机制与心血管疾病及心肌功能相关。心外膜脂肪组织表达具有炎症特征的蛋白质；然而，其相关机制尚待阐明。
本研究的目的是：1）检测冠状动脉疾病（CAD）患者和对照患者的心外膜与臀股部（大腿）配对脂肪组织中核因子-κB（NFκB）和c-Jun氨基末端激酶（JNK）信号通路的关键介质；2）调查CAD患者和对照受试者的循环内毒素水平。
从CAD患者（n = 16）和非CAD患者（n = 18）获取血清和脂肪组织活检样本（心外膜和大腿）。通过蛋白质印迹法、实时聚合酶链反应、酶联免疫吸附测定和活性研究对组织和血清样本中的炎症进行评估。
蛋白质印迹法显示，与大腿脂肪组织相比，心外膜脂肪组织中的NFκB、抑制性κB激酶（IKK）-γ、IKKβ以及JNK-1和JNK-2显著更高。心外膜mRNA数据显示，CD-68与Toll样受体-2、Toll样受体-4和肿瘤坏死因子-α之间存在强相关性。与匹配的对照相比，CAD患者的循环内毒素升高[CAD：6.80±0.28内毒素单位（EU）/毫升，对照组：5.52±0.57 EU/毫升；P<0.05]。
与CAD大腿脂肪组织和非CAD心外膜脂肪组织相比，CAD患者的心外膜脂肪组织中NFκB、IKKβ和JNK表达增加，表明对炎症存在特定部位以及与疾病相关的反应。这些研究表明NFκB和JNK信号通路均参与心外膜脂肪组织的炎症特征，并突出了巨噬细胞在该组织炎症中的作用。
