Haley K J, Lilly C M, Yang J H, Feng Y, Kennedy S P, Turi T G, Thompson J F, Sukhova G H, Libby P, Lee R T
Respiratory Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Circulation. 2000 Oct 31;102(18):2185-9. doi: 10.1161/01.cir.102.18.2185.
Unstable atherosclerotic lesions typically have an abundant inflammatory cell infiltrate, including activated T cells, macrophages, and mast cells, which may decrease plaque stability. The pathophysiology of inflammatory cell recruitment and activation in the human atheroma is incompletely described.
We hypothesized that differential gene expression with DNA microarray technology would identify new genes that may participate in vascular inflammation. RNA isolated from cultured human aortic smooth muscle cells treated with tumor necrosis factor-alpha (TNF-alpha) was examined with a DNA microarray with 8600 genes. This experiment and subsequent Northern analyses demonstrated marked increases in steady-state eotaxin mRNA (>20 fold), a chemokine initially described as a chemotactic factor for eosinophils. Because eosinophils are rarely present in human atherosclerosis, we then studied tissue samples from 7 normal and 14 atherosclerotic arteries. Immunohistochemical analysis demonstrated overexpression of eotaxin protein and its receptor, CCR3, in the human atheroma, with negligible expression in normal vessels. Eotaxin was predominantly located in smooth muscle cells. The CCR3 receptor was localized primarily to macrophage-rich regions as defined by immunopositivity for CD 68; a minority of mast cells also demonstrated immunopositivity for the CCR3 receptor.
Eotaxin and its receptor, CCR3, are overexpressed in human atherosclerosis, suggesting that eotaxin participates in vascular inflammation. These data demonstrate how genomic differential expression technology can identify novel genes that may participate in the stability of atherosclerotic lesions.
不稳定的动脉粥样硬化病变通常有大量炎性细胞浸润，包括活化的T细胞、巨噬细胞和肥大细胞，这可能会降低斑块稳定性。人类动脉粥样硬化中炎性细胞募集和活化的病理生理学尚未完全阐明。
我们推测，利用DNA微阵列技术进行差异基因表达分析能够识别出可能参与血管炎症的新基因。用肿瘤坏死因子-α（TNF-α）处理培养的人主动脉平滑肌细胞后分离出的RNA，通过含有8600个基因的DNA微阵列进行检测。该实验及随后的Northern分析表明，稳态嗜酸性粒细胞趋化因子mRNA显著增加（>20倍），嗜酸性粒细胞趋化因子是一种最初被描述为嗜酸性粒细胞趋化因子的趋化因子。由于嗜酸性粒细胞在人类动脉粥样硬化中很少出现，我们随后研究了7条正常动脉和14条动脉粥样硬化动脉的组织样本。免疫组织化学分析显示，嗜酸性粒细胞趋化因子蛋白及其受体CCR3在人类动脉粥样硬化斑块中过表达，而在正常血管中表达可忽略不计。嗜酸性粒细胞趋化因子主要位于平滑肌细胞中。CCR3受体主要定位于富含巨噬细胞的区域，该区域通过对CD 68的免疫阳性来界定；少数肥大细胞也显示出对CCR3受体的免疫阳性。
嗜酸性粒细胞趋化因子及其受体CCR3在人类动脉粥样硬化中过表达，提示嗜酸性粒细胞趋化因子参与血管炎症。这些数据证明了基因组差异表达技术如何能够识别出可能参与动脉粥样硬化病变稳定性的新基因。
