Localisation of mRNA for JE/MCP-1 and its receptor CCR2 in atherosclerotic lesions of the ApoE knockout mouse

Localisation of mRNA for JE/MCP-1 and its receptor CCR2 in atherosclerotic lesions of the ApoE knockout mouse
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DOI:
10.1159/000025720
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发表时间:
2000-03-01
影响因子:
1.7
通讯作者:
Reape, TJ
Reape, TJ
中科院分区:
医学4区
文献类型:
--
作者:
Rayner, K;Van Eersel, S;Reape, TJ

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MCP-1对单核细胞具有强的趋化活性,并与动脉粥样硬化的发病机制密切相关。在本研究中,我们已经使用原位杂交来检查JE的基因表达,MCP-1的小鼠同源物,和它的受体,CCR 2,在ApoE基因敲除小鼠动脉粥样硬化病变的发展过程中,有趣的是,最早的表达JE病变发展过程中检测到被发现定位于间充质细胞在外膜,而不是在内膜。随后发现巨噬细胞在这些受影响的外膜区域积聚,并且发现这些细胞表达高水平的JE。在这个阶段,早期巨噬细胞丰富的病变与高表达的JE也被认为是在内膜,但表达的JE受体(CCR 2)的mRNA只发现在外膜巨噬细胞,而不是在内膜。这一系列事件表明,外膜炎症可能是病变发展的重要早期事件,并可能通过从外膜以及通过血管腔募集导致内膜中巨噬细胞的后续蓄积。版权所有(C)2000 S. Karger AG,巴塞尔。
MCP-1 has potent chemotactic activity for monocytes and is strongly implicated in the pathogenesis of atherosclerosis. In the present study, we have used in situ hybridisation to examine the gene expression of JE, the murine homologue of MCP-1, and its receptor, CCR2, during the development of atherosclerotic lesions in the ApoE knockout mouse, interestingly, the earliest expression of JE detected during lesion development was found to be localised in mesenchymal cells in the adventitia and not in the intima. Macrophages were subsequently found to accumulate in these affected regions of the adventitia and these cells were found to express high levels of JE. At this stage, early macrophage-rich lesions with high expression of JE were also seen in the intima, but expression of mRNA for the receptor for JE (CCR2) was only found on adventitial macrophages and not in the intima. This sequence of events suggests that adventitial inflammation may be an important early event in lesion development and responsible for the subsequent accumulation of macrophages in the intima possibly by recruitment from the adventitia as well as via the vessel lumen. Copyright (C) 2000 S. Karger AG, Basel.