Porcine bioprosthetic valve calcification in bovine left ventricle-aorta shunts: studies of the deposition of vitamin K-dependent proteins.
Calcification of glutaraldehyde-preserved bioprosthetic cardiac valves represents a serious clinical problem. Previous work from this laboratory has established the presence in clinical bioprosthetic valve calcifications of vitamin K-dependent calcium-binding proteins, which contain the calcium-binding amino acid gamma-carboxyglutamic acid; no proteins containing gamma-carboxyglutamic acid are present in nonmineralized valves. The purpose of the present study was to examine a series of bovine circulatory bioprosthetic valve explants for calcification and proteins containing gamma-carboxyglutamic acid. Biochemical analyses of explanted bioprosthetic valves from calves demonstrated proteins with gamma-carboxyglutamic acid accumulating in calcified valves during both the onset and progression of valve calcification; calcium levels in the explanted calf bioprostheses were in the same range as those noted in clinical material. Accumulation of calcium and protein with gamma-carboxyglutamic acid occurred simultaneously and progressively, beginning 2 months after implantation. Small amounts of osteocalcin, the bone-derived protein containing gamma-carboxyglutamic acid, were present in both human and bovine bioprosthetic valve calcifications at comparable levels. No osteocalcin was detectable in non-mineralized valve tissue. Warfarin anticoagulant therapy did not prevent calcification or accumulation of protein with gamma-carboxyglutamic acid. It is concluded that proteins containing gamma-carboxyglutamic acid are involved in both the onset and progression of bioprosthetic valve calcification, and that conventional means of vitamin K antagonism do not alter this association or the course of bioprosthetic valve mineralization.
D015055:1-Carboxyglutamic Acid / Q000378:metabolism; D000293:Adolescent; D000818:Animals; D001021:Aortic Valve / Q000378:metabolism* / Q000601:surgery; D001705:Bioprosthesis; D002114:Calcinosis / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D006350:Heart Valve Prosthesis; D006801:Humans; D008297:Male; D015675:Osteocalcin; D011517:Prothrombin Time; D014859:Warfarin / Q000627:therapeutic use
D002135:Calcium-Binding Proteins; D015675:Osteocalcin; D015055:1-Carboxyglutamic Acid; D014859:Warfarin; D002118:Calcium