High Levels of Myeloid-Related Protein 14 in Human Atherosclerotic Plaques Correlate With the Characteristics of Rupture-Prone Lesions
High Levels of Myeloid-Related Protein 14 in Human Atherosclerotic Plaques Correlate With the Characteristics of Rupture-Prone Lesions
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DOI：
10.1161/atvbaha.109.190314
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发表时间：
2009-08-01
影响因子：
8.7
通讯作者：
de Kleijn, Dominique P. V.
中科院分区：
文献类型：
--
作者：
Ionita, Mihaela G.;Vink, Aryan;de Kleijn, Dominique P. V.
目的-动脉粥样硬化斑块破裂可导致心肌梗塞、中风等严重并发症。骨髓相关蛋白 (Mrp)-14、Mrp-8 和 Mrp-8/14 复合物是与心肌梗死相关的炎症标志物。然而，Mrps 是否与易破裂的斑块表型相关尚不清楚。在本研究中，我们确定了 Mrp-14、-8、-8/14 斑块水平与斑块特征之间的关联。方法和结果 - 在 186 个人类颈动脉斑块中，使用 ELISA 对 Mrp-14、-8 和 -8/14 水平进行定量。在脂质核心大、巨噬细胞染色高、平滑肌细胞和胶原蛋白含量低的病变中发现高水平的 Mrp-14。 Mrp-14 水平高的斑块含有高浓度的白细胞介素 (IL)-6、IL-8、基质金属蛋白酶 (MMP)-8、MMP-9 和低浓度的 MMP-2。 Mrp-8和Mrp-8/14表现出类似的趋势。在斑块内，非泡沫巨噬细胞的子集表达Mrp-8和Mrp-14，并且与稳定病变相比，易破裂病变中Mrp阳性巨噬细胞的百分比更高。在体外，当喂食 oxLDL 时，这部分巨噬细胞不会获得泡沫表型。 结论：Mrp-14 与易破裂动脉粥样硬化病变的组织病理学特征和炎症状态密切相关，将 Mrp-14 确定为这些斑块的局部标记物。 （动脉硬化血栓 Vasc Biol.2009；29：1220-1227。）
Objective-Atherosclerotic plaque rupture can lead to severe complications such as myocardial infarction and stroke. Myeloid related protein (Mrp)-14, Mrp-8, and Mrp-8/14 complex are inflammatory markers associated with myocardial infarction. It is, however, unknown whether Mrps are associated with a rupture-prone plaque phenotype. In this study, we determined the association between Mrp-14, -8, -8/14 plaque levels and plaque characteristics.Methods and Results-In 186 human carotid plaques, levels of Mrp-14, -8, and -8/14 were quantified using ELISA. High levels of Mrp-14 were found in lesions with a large lipid core, high macrophage staining, and low smooth muscle cell and collagen amount. Plaques with high levels of Mrp-14 contained high interleukin (IL)-6, IL-8, matrix metalloprotease (MMP)-8, MMP-9, and low MMP-2 concentrations. Mrp-8 and Mrp-8/14 showed a similar trend. Within plaques, a subset of nonfoam macrophages expressed Mrp-8 and Mrp-14 and the percentage of Mrp-positive macrophages was higher in rupture-prone lesions compared to stable ones. In vitro, this subset of macrophages does not acquire a foamy phenotype when fed oxLDL.Conclusion-Mrp-14 is strongly associated with the histopathologic features and the inflammatory status of rupture-prone atherosclerotic lesions, identifying Mrp-14 as a local marker for these plaques. (Arterioscler Thromb Vasc Biol. 2009; 29: 1220-1227.)