HMGB1 expression by activated vascular smooth muscle cells in advanced human atherosclerosis plaques
HMGB1 expression by activated vascular smooth muscle cells in advanced human atherosclerosis plaques
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DOI：
10.1016/j.carpath.2006.11.006
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发表时间：
2007-05-01
影响因子：
3.7
通讯作者：
Maruyama, Ikuro
中科院分区：
文献类型：
--
作者：
Inoue, Katsumi;Kawahara, Ko-ichi;Maruyama, Ikuro
背景：慢性炎症在动脉粥样硬化形成中起关键作用，其次是动脉粥样斑块不稳定性。高迁移率族蛋白I是由活化的巨噬细胞在长期炎症过程中作为晚期介质释放的。然而，高迁移率族蛋白I的表达及其对C反应蛋白和基质金属蛋白酶产生的影响，特别是在人血管平滑肌细胞上的表达仍不清楚。方法和结果：免疫组织化学研究显示，高迁移率族蛋白I在颈动脉和冠状动脉粥样斑块的血管平滑肌细胞中大量表达，而在纤维斑块的萎缩血管平滑肌细胞和正常的中膜血管平滑肌细胞中不表达。在高迁移率族蛋白1阳性的血管平滑肌细胞中也检测到晚期糖基化终产物受体。此外，高迁移率族蛋白I阳性的血管平滑肌细胞表达C反应蛋白和基质金属蛋白酶(2、3和9)。外源性高迁移率族蛋白I作用于培养的血管平滑肌细胞后，逆转录聚合酶链式反应和酶联免疫吸附试验均可显著提高C反应蛋白的表达水平。相反，免疫印迹检测显示，C-反应蛋白还能显著促进血管平滑肌细胞培养上清液中高迁移率族蛋白I的释放。结论：活化的血管平滑肌细胞是晚期动脉粥样硬化病变中高迁移率族蛋白I的来源。高迁移率族蛋白I通过晚期糖基化终产物受体直接刺激C反应蛋白和基质金属蛋白酶的产生。这些发现提供了新的证据，表明激活的血管平滑肌细胞产生的高迁移率族蛋白I可能有助于人类动脉粥样硬化病变向破裂的进展和易损性。(C)2007 Elsevier Inc.保留所有权利。
Background: Chronic inflammation plays a key role in atherogenesis, which is followed by atheromatous plaque instability. High-mobility group box I is released by activated macrophages as a late-phase mediator during prolonged inflammation. However, the expression of high-mobility group box I and its effect on the production of C-reactive protein and matrix metalloproteinases, particularly on human vascular smooth muscle cells, still remain unknown. Methods and results: Immunohistochemical studies revealed that high-mobility group box I was abundantly expressed in vascular smooth muscle cells of carotid and coronary atheromatous plaques, but not in atrophic vascular smooth muscle cells of fibrous plaques and normal medial vascular smooth muscle cells. Receptor for advanced glycation end products was also detected in vascular smooth muscle cells positive for high-mobility group box 1. Moreover, vascular smooth muscle cells positive for high-mobility group box I were found to express both C-reactive protein and matrix metalloproteinases (2, 3, and 9). Administration of exogenous high-mobility group box I to cultured vascular smooth muscle cells caused a marked elevation of C-reactive protein mRNA by reverse transcriptase-polymerase chain reaction and of C-reactive protein levels by enzyme-linked immunosorbent assay. Conversely, C-reactive protein also triggered a significant release of high-mobility group box I in vascular smooth muscle cell culture medium as determined by immunoblot. Conclusions: Activated vascular smooth muscle cells are the source of high-mobility group box I in human advanced atherosclerotic lesions. High-mobility group box I directly stimulates the production of both C-reactive protein and matrix metalloproteinase through receptor for advanced glycation end product. These findings provide new evidence that high-mobility group box I produced by activated vascular smooth muscle cells may contribute to the progression and vulnerability of human atherosclerotic lesions toward rupture. (c) 2007 Elsevier Inc. All rights reserved.