Relation of circulating matrix Gla-protein and anticoagulation status in patients with aortic valve calcification
Relation of circulating matrix Gla-protein and anticoagulation status in patients with aortic valve calcification
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DOI：
10.1160/th08-09-0611
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发表时间：
2009-04-01
影响因子：
6.7
通讯作者：
Schurgers, Leon J.
中科院分区：
文献类型：
--
作者：
Koos, Ralf;Krueger, Thilo;Schurgers, Leon J.
基质玻璃蛋白（MGP）是一种维生素K依赖性蛋白，可作为血管钙化的局部抑制剂。维生素K拮抗剂（口服抗凝剂; OAC）通过阻断维生素K代谢抑制MGP的活化。本研究的目的是研究长期OAC治疗对人体循环MGP水平和小鼠MGP表达的影响。此外，我们还检测了主动脉瓣疾病（AVD）患者中循环非活性MGP（ucMGP）水平与AVC的存在和严重程度之间的相关性。我们分析了191例经超声心动图证实的钙化AVD患者和35例对照组的循环ucMGP水平。通过多层螺旋CT评估患者的AVC范围。AVD患者的循环ucMGP水平（348.6 +/-123.1 nM）显著低于对照组（571.6 +/-153.9 nM，p <0.001）。在小鼠中测试香豆素的作用揭示了主动脉中MGP的mRNA表达也下调。多因素分析显示，肾小球滤过率和长期OAC治疗对患者组循环ucMGP水平有显著影响。随后，长期OAC患者的AVC评分显著增加。总之，与参考人群相比，钙化AVD患者的循环ucMGP水平显著较低，无冠状动脉和瓣膜钙化。此外，我们的数据表明，OAC治疗可能会降低MGR的局部表达，导致循环MGP水平降低，随后增加主动脉瓣钙化，这是一种不良副作用。
Matrix-Gla Protein (MGP) is a vitamin K-dependent protein acting as a local inhibitor of vascular calcification. Vitamin K-antagonists (oral anticoagulant;OAC) inhibit the activation of MGP by blocking vitamin K-metabolism. The aim of this study was to investigate the effect of long-term OAC treatment on circulating MGP levels in humans and on MGP expression in mice. Additionally, we tested the association between circulating inactive MGP (ucMGP) levels and the presence and severity of AVC in patients with aortic valve disease (AVD). We analysed circulating ucMGP levels in 19 1 consecutive patients with echocardiographically proven calcific AVD and 35 control subjects. The extent of AVC in the patients was assessed by multislice spiral computed tomography. Circulating ucMGP levels were significantly lower in patients with AVD (348.6 +/- 123.1 nM) compared to the control group (571.6 +/- 153.9 nM, p < 0.001). Testing the effect of coumarin in mice revealed that also the mRNA expression of MGP in the aorta was downregulated. Multifactorial analysis revealed a significant effect of glomerular filtration rate and long-term OAC therapy on circulating ucMGP levels in the patient group. Subsequently, patients on long-term OAC had significantly increased AVC scores. In conclusion, patients with calcific AVD had significantly lower levels of circulating ucMGP as compared to a reference population, free of coronary and valvular calcifications. In addition, our data suggest that OAC treatment may decrease local expression of MGR resulting in decreased circulating MGP levels and subsequently increased aortic valve calcifications as an adverse side effect.