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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1629.)
© 2005 American Heart Association, Inc.

Vascular Biology

Novel Conformation-Specific Antibodies Against Matrix -Carboxyglutamic Acid (Gla) Protein

Undercarboxylated Matrix Gla Protein as Marker for Vascular Calcification

Leon J. Schurgers; Kirsten J.F. Teunissen; Marjo H.J. Knapen; Martijn Kwaijtaal; Rob van Diest; Ad Appels; Chris P. Reutelingsperger; Jack P.M. Cleutjens; Cees Vermeer

From the Cardiovascular Research Institute (L.J.S., K.J.F.T., M.H.J.K., M.K., A.A., C.P.R., C.V.), VitaK (L.J.S., K.J.F.T., C.V.), and EURON, European Graduate School of Neuroscience (R.vD.), Maastricht University, the Netherlands; and the Department of Pathology (J.P.M.C.), University Hospital Maastricht, the Netherlands.

Correspondence to Dr L.J. Schurgers, Department of Biochemistry, University of Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands. E-mail l.schurgers{at}bioch.unimaas.nl

Objective— Matrix -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.

Methods and 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.

MGP is a strong inhibitor of arterial calcification; its function depends on vitamin K status. In this work, we demonstrate that: (1) undercarboxylated MGP is associated with arterial calcification, and (2) patients with angioplasty tend to have low serum MGP.

Key Words: matrix Gla protein (MGP) • vitamin K • calcification • atherosclerosis

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