Vitamin K-dependent Calcium Binding Proteins in Aortic Valve Calcification

Levy, Robert J.; Zenker, John A.; Lian, Jane B.

doi:10.1172/jci109700

Cited by 69 publications

(22 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the rat preparation of accelerated BC calcification in the present study levels of calcification in the control implants were comparable to those noted after 1 or more years of cinical implantation.' 35 Thus, the amount of diphosphonate compound required to inhibit the cuspal calcification process in the rat implants is probably comparable to a total dose that would be needed to inhibit calcification in a clinically implanted cusp.…”

Section: Resultsmentioning

confidence: 99%

Inhibition by diphosphonate compounds of calcification of porcine bioprosthetic heart valve cusps implanted subcutaneously in rats.

Levy¹,

Hawley²,

Schoen³

et al. 1985

Circulation

View full text Add to dashboard Cite

Calcification limits the long-term success of heart valve bioprostheses fabricated from glutaraldehyde cross-linked porcine aortic valves. The pathophysiology of calcification of bioprostheses has been studied experimentally with subcutaneous implants of the valve cusps in rats; in this preparation, the accumulation of calcific deposits is biochemically and morphologically identical to that occurring in clinical specimens. BIOPROSTHETIC cardiac valves (BCs) fabricated from glutaraldehyde-pretreated porcine aortic valve cusps'-3 or bovine pericardium4 6have assumed an important role in the surgical management of valvular heart disease, but calcification commonly causes their failure.7-10 The pathophysiology of this disease process has recently been reviewed" and was found to have the following features: The predominant morphology is one of intrinsic calcification, with mineral deposits located deep within the valve cusps in the central spongiosa region of the valve. 12-14 These deposits have been localized by electron microscopy in devitalized por-

show abstract

Section: Resultsmentioning

confidence: 99%

Inhibition by diphosphonate compounds of calcification of porcine bioprosthetic heart valve cusps implanted subcutaneously in rats.

Levy¹,

Hawley²,

Schoen³

et al. 1985

Circulation

View full text Add to dashboard Cite

show abstract

“…Previous reports have documented the presence of vitamin K-dependent ␥-carboxyglutamic acid containing proteins such as osteocalcin (bone Gla protein) in different types of pathologic calcification associated with atherosclerotic plaque and native and bioprosthetic valves (18,24,46,(64)(65)(66). Osteocalcin is secreted by osteoblasts and exhibits high affinity for calcium, phospholipid, and hydroxyapatite (34).…”

Section: Discussionmentioning

confidence: 99%

Increased cellular expression of matrix proteins that regulate mineralization is associated with calcification of native human and porcine xenograft bioprosthetic heart valves.

Srivatsa¹,

Harrity²,

Maercklein³

et al. 1997

J. Clin. Invest.

157

View full text Add to dashboard Cite

Dystrophic mineralization remains the leading cause of stenotic or regurgitant failure in native human and porcine bioprosthetic heart valves. We hypothesized that cellular expression of noncollagenous matrix proteins (osteopontin, osteocalcin, and osteonectin) that regulate skeletal mineralization may orchestrate valvular calcification.Porcine bioprosthetic heart valves and native human heart valves obtained during replacement surgery were analyzed for cells, matrix proteins that regulate mineralization, and vessels.Cell accumulation and calcification were correlated for both valve types (

show abstract

“…Aspartate and glutamate, which together comprised 21% of the amino acid residues in gallstone proteins, are also the major acidic amino acids in noncollagenous proteins of bone (22), in phosphophoryn, the acidic protein from dentin (22), and in proteins found in pathological cardiovascular calcifications (34,35). Highly acidic proteins, rich in aspartate and glutamate, have been found also in human urinary (23) and pancreatic (24) stones, which have been viewed as abnormal, ectopic biomineralization processes, regulated by these proteins (23,24).…”

Section: Discussionmentioning

confidence: 99%

Isolation of an acidic protein from cholesterol gallstones, which inhibits the precipitation of calcium carbonate in vitro.

Shimizu¹,

Sabsay²,

Veis³

et al. 1989

J. Clin. Invest.

View full text Add to dashboard Cite

In seeking to identify nucleating/antinucleating proteins involved in the pathogenesis of cholesterol gallstones, a major acidic protein was isolated from each of 13 samples of cholesterol gallstones. After the stones were extracted with methyl t-butyl ether to remove cholesterol, and methanol to remove bile salts and other lipids, they were demineralized with EDTA. The extracts were desalted with Sephadex-G25, and the proteins separated by PAGE. A protein was isolated, of molecular weight below 10 kD, which included firmly-bound diazo-positive yellow pigments and contained 24% acidic, but only 7% basic amino acid residues. The presence of N-acetyl glucosamine suggested that this was a glycoprotein. This protein at concentrations as low as 2 ,g/ml, but neither human serum albumin nor its complex with bilirubin, inhibited calcium carbonate precipitation from a supersaturated solution in vitro. This protein could be precipitated from 0.15 M NaCI solution by the addition of 0.5 M calcium chloride. Considering that cholesterol gallstones contain calcium and pigment at their centers, and that small acidic proteins are important regulators in other biomineralization systems, this protein seems likely to play a role in the pathogenesis of cholesterol gallstones.

show abstract

Vitamin K-dependent Calcium Binding Proteins in Aortic Valve Calcification

Cited by 69 publications

References 19 publications

Inhibition by diphosphonate compounds of calcification of porcine bioprosthetic heart valve cusps implanted subcutaneously in rats.

Inhibition by diphosphonate compounds of calcification of porcine bioprosthetic heart valve cusps implanted subcutaneously in rats.

Increased cellular expression of matrix proteins that regulate mineralization is associated with calcification of native human and porcine xenograft bioprosthetic heart valves.

Isolation of an acidic protein from cholesterol gallstones, which inhibits the precipitation of calcium carbonate in vitro.

Contact Info

Product

Resources

About