Vitamin K-Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis
Vitamin K-Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis
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DOI：
10.1681/asn.2016060651
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发表时间：
2017-06-01
影响因子：
13.6
通讯作者：
Malhotra, Rajeev
中科院分区：
文献类型：
--
作者：
Nigwekar, Sagar U.;Bloch, Donald B.;Malhotra, Rajeev
基质玻璃蛋白（MGP）是一种有效的血管钙化抑制剂。MGP抑制钙化的能力需要维生素k依赖性酶的活性，该酶介导MGP羧化。我们研究了MGP羧化如何影响接受透析的成年患者的钙化风险，并检查了维生素K缺乏对MGP羧化的影响。我们的研究包括20例接受血液透析伴钙化反应的患者（病例）和20例接受血液透析无钙化反应的患者（对照组），这些患者的年龄、性别、种族和华法林的使用相匹配。患者血浆中未羧化MGP （ucMGP）和羧化MGP （cMGP）水平均高于对照组。然而，羧化的MGP占总MGP的比例（cMGP相对浓度= cMGP/[cMGP +未羧化的MGM）在病例中低于对照组（分别为0.58+/-0.02和0.69+/-0.03，P=0.003）。在不服用华法林的患者中，患者的cMGP相对浓度同样较低。cMGP相对浓度每降低0.1个单位，钙化反应风险增加两倍以上。在多变量调整分析中，维生素K缺乏与较低的cMGP相对浓度相关（β =-8.99； P=0.04）。综上所述，维生素K缺乏介导的cMGP相对浓度降低可能在钙化反应的发病机制中起作用。是否补充维生素K可以预防和/或治疗钙化反应需要进一步的研究。
Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vitamin K deficiency on MGP carboxylation. Our study included 20 patients receiving hemodialysis with calciphylaxis (cases) and 20 patients receiving hemodialysis without calciphylaxis (controls) matched for age, sex, race, and warfarin use. Cases had higher plasma levels of uncarboxylated MGP (ucMGP) and carboxylated MGP (cMGP) than controls. However, the fraction of total MGP that was carboxylated (relative cMGP concentration = cMGP/[cMGP + uncarboxylated MGM) was lower in cases than in controls (0.58+/-0.02 versus 0.69+/-0.03, respectively; P=0.003). In patients not taking warfarin, cases had a similarly lower relative cMGP concentration. Each 0.1 unit reduction in relative cMGP concentration associated with a more than two-fold increase in calciphylaxis risk. Vitamin K deficiency associated with lower relative cMGP concentration in multivariable adjusted analyses (beta=-8.99; P=0.04). In conclusion, vitamin K deficiency-mediated reduction in relative cMGP concentration may have a role in the pathogenesis of calciphylaxis. Whether vitamin K supplementation can prevent and/or treat calciphylaxis requires further study.