Human epicardial adipose tissue is a source of inflammatory mediators

Human epicardial adipose tissue is a source of inflammatory mediators
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DOI:
10.1161/01.cir.0000099542.57313.c5
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发表时间:
2003-11-18
期刊:
影响因子:
37.8
通讯作者:
Shi, Y
Shi, Y
中科院分区:
医学1区
文献类型:
--
作者:
Mazurek, T;Zhang, LF;Shi, Y

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背景:血管和血管外组织产生的炎症介质促进冠状动脉病变的形成。脂肪组织可能作为一种内分泌器官发挥作用,在有心血管并发症风险的患者中导致炎症负担。在这项研究中,我们试图比较表达的炎症介质在心外膜和皮下脂肪储存在患者的关键CAD.Methods和结果配对样本的心外膜和皮下脂肪组织收集在开始选择性冠状动脉旁路移植术(n=42;年龄65+/-10岁)。通过TaqMan实时逆转录-聚合酶链反应(mRNA)和ELISA(3小时内蛋白释放)分析趋化因子(单核细胞趋化蛋白[MCP]-1)和炎性细胞因子(白细胞介素[IL]-1 β、IL-6和肿瘤坏死因子[TNF]-α)的局部表达。在心外膜脂肪储备中观察到显著更高水平的IL-1 β、IL-6、MCP-1和TNF-α mRNA和蛋白。无论临床变量(糖尿病、体重指数和长期使用他汀类药物或ACE抑制剂/血管紧张素II受体阻滞剂)或循环生物标志物的血浆浓度如何,均观察到心外膜脂肪组织的促炎特性。在一组样本(n=11)中,通过DNA微阵列杂交探索了全局基因表达,并证实了冠状动脉疾病患者心外膜脂肪组织中存在广泛的炎症反应。上述研究结果被证实存在炎性细胞浸润在心外膜脂肪stores.Conclusions-Epicardial脂肪组织是一个来源的几个炎症介质在高危心脏病患者。血浆炎症生物标志物可能无法充分反映局部组织炎症。目前的治疗似乎不能消除心外膜脂肪组织中的局部炎症信号。
Background-Inflammatory mediators that originate in vascular and extravascular tissues promote coronary lesion formation. Adipose tissue may function as an endocrine organ that contributes to an inflammatory burden in patients at risk of cardiovascular complications. In this study, we sought to compare expression of inflammatory mediators in epicardial and subcutaneous adipose stores in patients with critical CAD.Methods and Results-Paired samples of epicardial and subcutaneous adipose tissues were harvested at the outset of elective CABG surgery (n=42; age 65+/-10 years). Local expression of chemokine (monocyte chemotactic protein [MCP]-1) and inflammatory cytokines (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha) was analyzed by TaqMan real-time reverse transcription-polymerase chain reaction (mRNA) and by ELISA (protein release over 3 hours). Significantly higher levels of IL-1beta, IL-6, MCP-1, and TNF-alpha mRNA and protein were observed in epicardial adipose stores. Proinflammatory properties of epicardial adipose tissue were noted irrespective of clinical variables (diabetes, body mass index, and chronic use of statins or ACE inhibitors/angiotensin II receptor blockers) or plasma concentrations of circulating biomarkers. In a subset of samples (n=11), global gene expression was explored by DNA microarray hybridization and confirmed the presence of a broad inflammatory reaction in epicardial adipose tissue in patients with coronary artery disease. The above findings were paralleled by the presence of inflammatory cell infiltrates in epicardial adipose stores.Conclusions-Epicardial adipose tissue is a source of several inflammatory mediators in high-risk cardiac patients. Plasma inflammatory biomarkers may not adequately reflect local tissue inflammation. Current therapies do not appear to eliminate local inflammatory signals in epicardial adipose tissue.