Tenascin-C is expressed in macrophage-rich human coronary atherosclerotic plaque.
Tenascin-C is expressed in macrophage-rich human coronary atherosclerotic plaque.
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DOI：
10.1161/01.cir.99.10.1284
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发表时间：
1999-03
期刊：
影响因子：
37.8
通讯作者：
K. Wallner;Chen Li;P. Shah;M. Fishbein;J. Forrester;S. Kaul;B. Sharifi
中科院分区：
文献类型：
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作者：
K. Wallner;Chen Li;P. Shah;M. Fishbein;J. Forrester;S. Kaul;B. Sharifi
研究背景：Tenascin是一种大的细胞外基质糖蛋白，广泛存在于创伤愈合和肿瘤愈合等活动性重塑的成人组织中。为了探讨TN-C在动脉粥样硬化发病机制中的作用，我们研究了TN-C在人冠状动脉斑块中的表达模式。方法和结果免疫组织化学染色和原位杂交显示TN-C在纤维化但脂质缺乏的动脉粥样硬化斑块中有少量随机表达。相反，所有有组织的脂核或内膜表面破裂的斑块都强烈表达TN-C，TN-C优先集中在脂核、肩部和斑块破裂区周围，而不是纤维帽。正常动脉组织中未检测到TN-C。为了确定TN-C的细胞来源，用平滑肌细胞和巨噬细胞特异性抗体对斑块进行了染色。TN-C的表达与巨噬细胞的浸润有关。Northern印迹和免疫沉淀分析表明，巨噬细胞表达7.0kb的TN-C mRNA和220 kDa的蛋白。逆转录-聚合酶链式反应显示巨噬细胞表达TN-C的小亚型。酶谱分析显示巨噬细胞显著增加了基质金属蛋白酶-9的表达。结论TN-C的表达水平与炎症程度相关，与斑块大小无关。此外，培养的巨噬细胞具有表达TN-C基因的能力。这些发现提示巨噬细胞在动脉粥样硬化斑块基质成分重塑中的意义。
BACKGROUND Tenascin is a large extracellular matrix glycoprotein generally found in adult tissues undergoing active remodeling such as healing wounds and tumors. To determine the potential role of tenascin-C (TN-C) in the pathophysiology of atherosclerosis, we investigated the pattern of expression of TN-C in human coronary atherosclerotic plaques. METHODS AND RESULTS Immunohistochemical staining and in situ hybridization demonstrated minimal and random expression of TN-C in fibrotic but lipid-poor atherosclerotic plaques. In contrast, all plaques with an organized lipid core or ruptured intimal surface strongly expressed TN-C, which was preferentially concentrated around the lipid core, shoulder regions, and ruptured area of the plaques but not in the fibrous cap. TN-C was not detected in normal arterial tissue. To identify the cellular source of TN-C, the plaques were stained with smooth muscle cell- and macrophage-specific antibodies. TN-C expression correlated with the infiltration of macrophages. Northern blot and immunoprecipitation analysis showed that macrophages expressed 7. 0-kb TN-C mRNA and 220-kDa protein. Reverse transcription-polymerase chain reaction of total RNA derived from macrophages showed that they express the small isoform of TN-C. Zymogram analysis revealed that macrophages markedly increased MMP-9 expression. CONCLUSIONS This study demonstrates that the level of TN-C expression correlates with the degree of inflammation present, not with plaque size. In addition, cultured macrophages have the capacity to express the TN-C gene. These findings suggest the significance of macrophages in the remodeling of atherosclerotic plaque matrix composition.