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他汀类药物与血液凝固

Statins and blood coagulation.

作者信息

Undas Anetta, Brummel-Ziedins Kathleen E, Mann Kenneth G

机构信息

Department of Medicine, Jagiellonian University School of Medicine, Krakow, Poland.

出版信息

Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):287-94. doi: 10.1161/01.ATV.0000151647.14923.ec. Epub 2004 Nov 29.

Abstract

The 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) have been shown to exhibit several vascular protective effects, including antithrombotic properties, that are not related to changes in lipid profile. There is growing evidence that treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation. Accordingly, statin use has been associated with impairment of several coagulant reactions catalyzed by this enzyme. Moreover, evidence indicates that statins, via increased thrombomodulin expression on endothelial cells, may enhance the activity of the protein C anticoagulant pathway. Most of the antithrombotic effects of statins are attributed to the inhibition of isoprenylation of signaling proteins. These novel properties of statins, suggesting that these drugs might act as mild anticoagulants, may explain, at least in part, the therapeutic benefits observed in a wide spectrum of patients with varying cholesterol levels, including subjects with acute coronary events. The HMG-CoA reductase inhibitors (statins) have been shown to exhibit several vascular protective effects, including antithrombotic properties, that are not related to changes in lipid profile. Treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation.

摘要

3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂(他汀类药物)已被证明具有多种血管保护作用,包括抗血栓形成特性,这些作用与血脂水平的变化无关。越来越多的证据表明,他汀类药物治疗可导致凝血级联反应显著下调,这很可能是组织因子表达降低的结果,进而导致凝血酶生成减少。因此,使用他汀类药物与该酶催化的几种凝血反应受损有关。此外,有证据表明,他汀类药物通过增加内皮细胞上血栓调节蛋白的表达,可能增强蛋白C抗凝途径的活性。他汀类药物的大多数抗血栓形成作用归因于对信号蛋白异戊二烯化的抑制。他汀类药物的这些新特性表明这些药物可能起到轻度抗凝剂的作用,这至少可以部分解释在包括急性冠脉事件患者在内的广泛胆固醇水平不同的患者中观察到的治疗益处。3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂(他汀类药物)已被证明具有多种血管保护作用,包括抗血栓形成特性,这些作用与血脂水平的变化无关。他汀类药物治疗可导致凝血级联反应显著下调,这很可能是组织因子表达降低的结果,进而导致凝血酶生成减少。

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