Vascular calcification: expression patterns of the osteoblast-specific gene core binding factor alpha-1 and the protective factor matrix gla protein in human atherogenesis.
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.
Engelse
M A
MA
Department of Biochemistry, Academic Medical Center K1-163, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.
Neele
J M
JM
Bronckers
A L
AL
Pannekoek
H
H
de Vries
C J
CJ
D001161:Arteriosclerosis / Q000378:metabolism*; D002114:Calcinosis / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000032:analysis* / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D050660:Core Binding Factors; D004730:Endothelium, Vascular / Q000737:chemistry*; D016326:Extracellular Matrix Proteins; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008264:Macrophages / Q000737:chemistry*; D009131:Muscle, Smooth, Vascular / Q000737:chemistry*; D009363:Neoplasm Proteins; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D000097568:Matrix Gla Protein
D002135:Calcium-Binding Proteins; D050660:Core Binding Factors; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000097568:Matrix Gla Protein