Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification

Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1629-33. doi: 10.1161/01.ATV.0000173313.46222.43. Epub 2005 Jun 16.

Abstract

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Specificity*
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Biomarkers / chemistry
  • Biomarkers / metabolism
  • Calcinosis / metabolism*
  • Calcinosis / pathology
  • Calcium-Binding Proteins / blood
  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / immunology*
  • Epitopes / chemistry
  • Epitopes / immunology
  • Epitopes / metabolism
  • Extracellular Matrix Proteins / blood
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / immunology*
  • Humans
  • Immunohistochemistry / methods*
  • Monckeberg Medial Calcific Sclerosis / metabolism
  • Monckeberg Medial Calcific Sclerosis / pathology
  • Protein Conformation
  • Tunica Intima / metabolism
  • Tunica Intima / pathology
  • Tunica Media / metabolism
  • Tunica Media / pathology
  • Vitamin K / metabolism

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Epitopes
  • Extracellular Matrix Proteins
  • matrix Gla protein
  • Vitamin K