Characterization of a Gla-containing protein from calcified human atherosclerotic plaques.

Abstract

In this article we describe the isolation of a 4-carboxyglutamic acid (Gla)-containing protein from calcified human atherosclerotic plaques. The protein was extracted from pulverized calcified plaques by demineralization with ethylenediaminetetraacetate and was subsequently purified by anion-exchange fast protein and highperformance liquid chromatography by using ion-exchange and gel-filtration columns. The protein was designated as plaque Gla protein (PGP) and has an apparent mass of 23 kD as estimated from sodium dodecyl sulfate-polyacrylamide gel analysis. By determining the sequence of its first six amino acid residues, the protein was unequivocally demonstrated to be not related to any other known protein.Moreover, no immunological relationship (as tested by Western blot analysis) was found between PGP and other known Gla-containing proteins. (Arteriosclerosis 10:991-995, November/December 1990)

Noncollagenous Bone Matrix Proteins, Calcification, and Thrombosis in Carotid Artery Atherosclerosis

“…6,23,25,26,60 Although osteocalcin has been extracted from atherosclerotic plaques, 31,32 we did not detect it associated with any cell types in any of the atheromas examined. Because in this work we have shown that osteocalcin colocalized with fibrin II/calcium deposits, it might be derived from plasma and/or platelets.…”

Diffuse calcification in human coronary arteries. Association of osteopontin with atherosclerosis.

“…Osteocalcin, a protein containing Gla-residues (28) has been extracted from human calcified arterial plaques (29). An additional calcium-binding Gla-containing protein named plaque Gla protein (PGP) was isolated from human calcified plaque (30). Osteocalcin plays an essential role in normal skeleton development, and genderrelated differences in skeletal tissue suggest that this phosphorylated glycoprotein may play an important role in the pathogenesis of several disorders (31 ).…”

“…Gamma carboxyglutamate, or Gla, is an amino acid residue with a high affinity for binding hydroxy-apatite. Gijsbers and co-workers have indicated that gamma-glutamate carboxylase activity is increased in normal arteries as compared to atherosclerotic vessels (30). In the normal vessel, therefore, Gla proteins may prevent the deposition of hydroxyapatite into the vessel wall (6); thus the in vivo and in vitro roles for the Gla proteins remain unclear.…”

Age-related medial elastocalcinosis in arteries: mechanisms, animal models, and physiological consequences

“…There exists, therefore, a number of proteins that chelate or sequester these ions (essentially calcium), thus lessening their availability and the possibility of precipitation (38,105). The use of mutated mouse models has revealed the existence of a number of inhibitors of calcification: matrix Gla proteins, osteopontin, pyrophosphate, ␤-glucosidase, carbonic anhydrase II, fetuin-A, desmin, osteoprotegerin (OPG), and Smad 6 (37).…”