Matrix Gla protein accumulates at the border of regions of calcification and normal tissue in the media of the arterial vessel wall.
Vitamin K-dependent matrix Gla protein (MGP) has been suggested to play a role in the inhibition of soft-tissue calcification. Here we report the expression of recombinant prokaryotic MGP as part of a fusion protein and the preparation of two antibodies that specifically recognize MGP. Monoclonal antibodies were raised against synthetic peptides homologous to the sequences 3-15 and 63-75 of human MGP. Both antibodies recognize recombinant and synthetic human MGP. Immunohistochemical analysis showed that MGP was associated with the extracellular matrix of noncalcified bone and with chondrocytes in cartilage. In the healthy human arterial vessel wall, MGP antigen was demonstrated in association with smooth muscle cells and elastic laminae of the tunica media and with the extracellular matrix of the adventitia. Colocalization with the elastic laminae was lost at sites of medial calcification; in both human and rat arteries, high amounts of MGP were found in the extracellular matrix at borders of intimal and medial calcification. Our data demonstrate the close association between MGP and calcification. It is suggested that undercarboxylated MGP is biologically inactive and that poor vascular vitamin K status may form a risk factor for vascular calcification.
Spronk
H M
HM
Department of Biochemistry, Maastricht University, Maastricht, The Netherlands.
Soute
B A
BA
Schurgers
L J
LJ
Cleutjens
J P
JP
Thijssen
H H
HH
De Mey
J G
JG
Vermeer
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D001485:Basement Membrane / Q000378:metabolism; D015153:Blotting, Western; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D019902:Chondrocytes / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015675:Osteocalcin / Q000096:biosynthesis / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism; D014812:Vitamin K / Q000378:metabolism; D000097568:Matrix Gla Protein
D000911:Antibodies, Monoclonal; D002118:Calcium; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D015675:Osteocalcin; D012313:RNA; D011994:Recombinant Proteins; D014812:Vitamin K; D000097568:Matrix Gla Protein