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华法林相关性血管钙化及其可能的治疗方法的研究进展。

Research progress of warfarin-associated vascular calcification and its possible therapy.

机构信息

Department of Pharmacology, Dalian Medical University, Dalian, People's Republic of China.

出版信息

J Cardiovasc Pharmacol. 2014 Jan;63(1):76-82. doi: 10.1097/FJC.0000000000000008.

Abstract

Vascular calcification is a common comorbidity in elderly patients with diabetes mellitus or renal insufficiency. A large number of studies have shown that vascular calcification can be induced and accelerated in patients undergoing long-term treatment with warfarin, leading to some severe complications, such as hypertension, atherosclerosis, valvular calcification, and coronary calcification, especially in the population with atrial fibrillation, hemodialysis, and chronic kidney disease. Warfarin inhibits the activation of vitamin K-dependent coagulation factors and affects the function of vitamin K-dependent proteins via interference of the vitamin K cycle by antagonizing vitamin K. One of its consequences is adverse effects on the expression and function of matrix Gla protein, one of the important vitamin K-dependent proteins. Matrix Gla protein acts as an inhibitor of vascular calcification by blocking bone morphogenetic protein signaling or promoting the phagocytosis of apoptotic bodies; moreover, it restrains the formation of calcification directly resulting in the promotion of vascular calcification. This article also discusses the various treatments for vascular calcification caused by warfarin.

摘要

血管钙化是老年糖尿病或肾功能不全患者的常见合并症。大量研究表明,华法林长期治疗可诱导和加速患者发生血管钙化,导致一些严重并发症,如高血压、动脉粥样硬化、瓣膜钙化和冠状动脉钙化,尤其是在心房颤动、血液透析和慢性肾脏病患者中。华法林通过拮抗维生素 K 抑制维生素 K 环来抑制维生素 K 依赖性凝血因子的激活,并通过干扰维生素 K 依赖性蛋白的功能。其后果之一是对基质 Gla 蛋白(一种重要的维生素 K 依赖性蛋白)的表达和功能产生不良影响。基质 Gla 蛋白通过阻断骨形态发生蛋白信号或促进细胞凋亡小体的吞噬作用来抑制血管钙化;此外,它还直接抑制钙化的形成,从而促进血管钙化。本文还讨论了华法林引起的血管钙化的各种治疗方法。

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