Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification.
OBJECTIVE
Matrix gamma-carboxyglutamic acid (Gla) protein (MGP), a vitamin K-dependent protein, is a potent in vivo inhibitor of arterial calcification. We hypothesized that low endogenous production of MGP and impaired carboxylation of MGP may contribute to the development or the progression of vascular disease.


RESULTS
Novel conformation-specific antibodies against MGP were used for immunohistochemistry of healthy and sclerotic arteries. In healthy arteries, MGP was mainly displayed around the elastin fibers in the tunica media. The staining colocalized with that for carboxylated MGP, whereas undercarboxylated MGP (ucMGP) was not detected. In atherosclerotic arteries, ucMGP was found in the intima, where it was associated with vesicular structures. In Mönckeberg's sclerosis of the media, ucMGP was localized around all areas of calcification. The results indicate that ucMGP is strongly associated with vascular calcification of different etiologies. In a separate study, serum MGP concentrations in a cohort of 172 subjects who had undergone percutaneous coronary intervention were significantly reduced compared with an apparently healthy population.


CONCLUSIONS
These data show that impaired carboxylation of MGP is associated with intimal and medial vascular calcification and suggest the essentiality of the vitamin K modification to the function of MGP as an inhibitor of ectopic calcification.
Schurgers
Leon J
LJ
Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands. l.schurgers@bioch.unimaas.nl
Teunissen
Kirsten J F
KJ
Knapen
Marjo H J
MH
Kwaijtaal
Martijn
M
van Diest
Rob
R
Appels
Ad
A
Reutelingsperger
Chris P
CP
Cleutjens
Jack P M
JP
Vermeer
Cees
C
D000918:Antibody Specificity; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D050380:Monckeberg Medial Calcific Sclerosis / Q000378:metabolism / Q000473:pathology; D011487:Protein Conformation; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology; D014812:Vitamin K / Q000378:metabolism; D000097568:Matrix Gla Protein
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D014812:Vitamin K; D000097568:Matrix Gla Protein