Strong induction of members of the chitinase family of proteins in atherosclerosis - Chitotriosidase and human cartilage gp-39 expressed in lesion macrophages
Strong induction of members of the chitinase family of proteins in atherosclerosis - Chitotriosidase and human cartilage gp-39 expressed in lesion macrophages
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DOI：
10.1161/01.atv.19.3.687
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发表时间：
1999-03-01
影响因子：
8.7
通讯作者：
de Vries, CJM
中科院分区：
文献类型：
--
作者：
Boot, RG;van Achterberg, TAE;de Vries, CJM
动脉粥样硬化是由单核细胞浸润到血管壁的内皮下空间和随后的激活的巨噬细胞的脂质积累引发的。巨噬细胞在动脉粥样硬化形成中异常行为的分子机制仅部分被揭示。壳三糖苷酶和人软骨gp-39（HC gp-39）是几丁质酶蛋白家族的成员，在戈谢病期间在各种器官中积累的充满脂质的巨噬细胞中表达。此外，如本研究所示，在培养的巨噬细胞中，壳三糖苷酶和HC gp-39可以以不同的动力学诱导。我们研究了这些几丁质酶样基因的表达在人类动脉粥样硬化血管壁的原位杂交标本来自股动脉（4个标本），主动脉（4个标本），髂动脉（3个标本），颈动脉（4个标本），冠状动脉（1个标本），以及5个标本来自明显正常的血管组织。我们第一次表明，壳三糖苷酶和HC gp-39的表达强烈上调，在不同的亚群的巨噬细胞在动脉粥样硬化斑块。壳三糖苷酶和HC gp-39的表达模式进行了比较，并显示出与观察到的细胞外基质蛋白骨桥蛋白和巨噬细胞标志物抗酒石酸酸性磷酸酶的模式不同。我们的数据强调了动脉粥样硬化病变中巨噬细胞的显著表型变异。此外，在动脉粥样硬化组织的提取物中，壳三糖苷酶的酶活性被证明升高高达55倍。虽然壳三糖苷酶和HC gp-39的功能尚未确定，我们假设在动脉粥样硬化形成过程中的细胞迁移和组织重塑的作用。
Atherosclerosis is initiated by the infiltration of monocytes into the subendothelial space of the vessel wall and subsequent lipid accumulation of the activated macrophages. The molecular mechanisms involved in the anomalous behavior of macrophages in atherogenesis have only partially been disclosed. Chitotriosidase and human cartilage gp-39 (HC gp-39) are members of the chitinase family of proteins and are expressed in lipid-laden macrophages accumulated in various organs during Gaucher disease. In addition, as shown in this study, chitotriosidase and HC gp-39 can be induced with distinct kinetics in cultured macrophages. We investigated the expression of these chitinase-like genes in the human atherosclerotic vessel wall by in situ hybridizations on atherosclerotic specimens derived from femoral artery (4 specimens), aorta (4 specimens), iliac artery (3 specimens), carotid artery (4 specimens), and coronary artery (1 specimen), as well as 5 specimens derived from apparently normal vascular tissue. We show for the first time that chitotriosidase and HC gp-39 expression was strongly upregulated in distinct subsets of macrophages in the atherosclerotic plaque. The expression patterns of chitotriosidase and HC gp-39 were compared and shown to be different from the patterns observed for the extracellular matrix protein osteopontin and the macrophage marker tartrate-resistant acid phosphatase. Our data emphasize the remarkable phenotypic variation among macrophages present in the atherosclerotic lesion. Furthermore, chitotriosidase enzyme activity was shown to be elevated up to 55-fold in extracts of atherosclerotic tissue. Although a function for chitotriosidase and HC gp-39 has not been identified, we hypothesize a role in cell migration and tissue remodeling during atherogenesis.