Levy R J, Zenker J A, Bernhard W F
Ann Thorac Surg. 1983 Aug;36(2):187-92. doi: 10.1016/s0003-4975(10)60454-7.
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.
戊二醛保存的生物人工心脏瓣膜钙化是一个严重的临床问题。本实验室之前的研究已证实，临床生物人工瓣膜钙化中存在维生素K依赖的钙结合蛋白，这些蛋白含有钙结合氨基酸γ-羧基谷氨酸；非矿化瓣膜中不存在含γ-羧基谷氨酸的蛋白。本研究的目的是检查一系列牛循环生物人工瓣膜外植体的钙化情况以及含γ-羧基谷氨酸的蛋白。对小牛的生物人工瓣膜外植体进行生化分析表明，在瓣膜钙化的起始和进展过程中，含γ-羧基谷氨酸的蛋白在钙化瓣膜中积累；小牛生物人工瓣膜外植体中的钙水平与临床材料中的水平范围相同。钙和含γ-羧基谷氨酸的蛋白同时并逐渐积累，在植入后2个月开始。在人和牛的生物人工瓣膜钙化中均存在少量骨钙素，即含γ-羧基谷氨酸的骨源性蛋白，且水平相当。在非矿化瓣膜组织中未检测到骨钙素。华法林抗凝治疗并不能预防钙化或含γ-羧基谷氨酸的蛋白的积累。得出的结论是，含γ-羧基谷氨酸的蛋白参与了生物人工瓣膜钙化的起始和进展，并且传统的维生素K拮抗方法不会改变这种关联或生物人工瓣膜矿化的进程。
