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脂肪组织促炎基因表达与心血管疾病有关。

Adipose tissue pro-inflammatory gene expression is associated with cardiovascular disease.

机构信息

Centre for Clinical Heart Research, Oslo University Hospital Ulleval, Oslo, Norway.

出版信息

Int J Clin Pract. 2011 Sep;65(9):939-44. doi: 10.1111/j.1742-1241.2011.02717.x.

Abstract

BACKGROUND

Obese patients are at high risk of developing cardiovascular disease. Several studies suggest obesity as an independent risk factor. Adipose tissue is now accepted as an endocrine organ that produces and secretes a variety of cytokines, hormones and other metabolic players involved in the pathogenesis of atherosclerosis. Among this versatile group of mediators and effectors of inflammation and atherothrombosis, we have studied the expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor-1 (PAI-1), interleukin-18 (IL-18) and interleukin-6 (IL-6). All these markers, in their circulatory form, have been associated with cardiovascular disease. However, there is no much data available on their expression in adipose tissue in human subjects with and without cardiovascular disease.

MATERIAL AND METHODS

We successfully isolated RNA from subcutaneous fat biopsies of 61 patients with or without cardiovascular disease. We then measured the RNA expression of MMP-9, TIMP-1, PAI-1, IL-18 and IL-6 with Real-Time PCR, using relative quantification.

RESULTS

Albeit not statistically significant, all inflammatory mediators - except IL-18 - were highly expressed in patients with cardiovascular disease (n = 16) compared with those without (n = 45). Pooling the gene expression data, trying to capture the overall inflammatory activity in adipose tissue in a score system, we observed a highly significant association with CVD.

CONCLUSIONS

Trying to capture the overall inflammatory activity, in addition to the mass of adipose tissue, could provide useful hints towards a pathogenetic link between obesity and presence of cardiovascular disease.

摘要

背景

肥胖患者罹患心血管疾病的风险很高。有几项研究提示肥胖是一个独立的危险因素。脂肪组织现在被认为是一种内分泌器官,可产生和分泌多种细胞因子、激素和其他代谢因子,参与动脉粥样硬化的发病机制。在这组多功能的炎症和动脉粥样硬化形成的介质和效应物中,我们研究了基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)、纤溶酶原激活物抑制剂-1(PAI-1)、白细胞介素-18(IL-18)和白细胞介素-6(IL-6)的表达。所有这些标志物以其循环形式与心血管疾病相关。然而,关于它们在有或无心血管疾病的人类受试者脂肪组织中的表达,数据并不多。

材料和方法

我们成功地从 61 例有或无心血管疾病的患者的皮下脂肪活检组织中分离出 RNA。然后,我们使用实时 PCR 用相对定量法测量 MMP-9、TIMP-1、PAI-1、IL-18 和 IL-6 的 RNA 表达。

结果

虽然没有统计学意义,但与没有心血管疾病的患者(n = 45)相比,所有炎症介质(除了 IL-18 外)在患有心血管疾病的患者(n = 16)中表达水平均较高。汇总基因表达数据,试图在评分系统中捕获脂肪组织中的整体炎症活性,我们观察到与 CVD 高度相关。

结论

试图捕捉整体炎症活性,除了脂肪组织的质量外,可能为肥胖与心血管疾病存在之间的发病机制联系提供有用的线索。

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