Vascular calcification:: expression patterns of the osteoblast-specific gene core binding factor α-1 and the protective factor matrix gla protein in human atherogenesis

被引:108
作者
Engelse, MA
Neele, JA
Bronckers, ALJJ
Pannekoek, H
de Vries, CJM
机构
[1] Univ Amsterdam, Acad Med Ctr K1163, NL-1105 AZ Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Dept Oral Cell Biol, ACTA, Amsterdam, Netherlands
关键词
atherosclerosis; gene expression; macrophages; smooth muscle; extracellular matrix;
D O I
10.1016/S0008-6363(01)00375-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Increasing evidence suggests that vascular calcification is a regulated process. We studied the vascular expression pattern of a key factor in mineralization and a counteracting, protective factor. Based on the phenotype of null mice, Core binding factor alpha-1 (Cbfa-1) plays a pivotal role in bone formation, whereas Matrix Gla Protein (MGP) is a potent inhibitor of vascular calcification. Methods: We investigated the expression of MGP and Cbfa-1 in cultured, human monocytic cells, endothelial cells and smooth muscle cells (SMC), as well as in normal and atherosclerotic vessel specimens. Results: In cultured cells MGP is expressed in endothelial cells and SMC, whereas Cbfa-1 mRNA is predominantly present in macrophages and to a lesser extent in SMC. In the normal vessel wall MGP expression is high at the luminal side and declines toward the center of the media, whereas Cbfa-1 is absent. Moderate, diffuse calcification of the aorta media was observed only in those regions where MGP is low or absent. In atherosclerotic lesions MGP is expressed in endothelial cells and SMC that form fibrous caps, but is never present in macrophages. Cbfa-1 is synthesized in regions without MGP, it is associated with calcified areas and Cbfa-1 may be considered a marker for osteoprogenitor-like cells in the vessel wall. Conclusions: Our observations on MGP expression confirm and extend published data and are consistent with a protective function of MGP. Cbfa-1 expression is absent in normal medial SMC and co-localizes with neointimal macrophages and focal calcifications. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:281 / 289
页数:9
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