Antithrombotic properties of pravastatin reducing intra-thrombus fibrin deposition under high shear blood flow conditions
Antithrombotic properties of pravastatin reducing intra-thrombus fibrin deposition under high shear blood flow conditions
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DOI：
10.1160/th10-09-0587
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发表时间：
2011-02-01
影响因子：
6.7
通讯作者：
Shima, Midori
中科院分区：
文献类型：
--
作者：
Hamada, Masaaki;Sugimoto, Mitsuhiko;Shima, Midori
除了降低胆固醇，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）具有一系列多效性作用，有助于降低不良心血管事件的风险。我们试图了解他汀类药物在生理性全血流动条件下发挥抗血小板作用的分子机制。使用体外灌注室系统，我们研究了普伐他汀在高或低剪切率的全血流条件下的抗血小板作用。我们确定，普伐他汀显着抑制血小板活化依赖性促凝血活性，降低P-选择素膜的表达，组织因子的积累，并在高剪切速率条件下产生的血管性血友病因子表面上的血小板血栓内的凝血酶结合。这些作用导致血栓内纤维蛋白沉积减少。这些抗血栓性质的普伐他汀，这是阿托伐他汀，可以废除甲羟戊酸。我们的实验方法揭示了一种新的机制介导的抗血小板作用的他汀类药物。剪切率依赖性抗血栓形成活性可以解释普伐他汀对降低体内高剪切率全血流条件下通常发生的心血管事件的有利作用。
In addition to lowering cholesterol, the 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) have a range of pleiotropic effects that help reduce the risk of adverse cardiovascular events. We sought to understand the molecular mechanisms by which statins could exert anti-platelet actions under physiologic whole blood flow conditions. Using an in vitro perfusion chamber system, we examined the anti-platelet effects of pravastatin under whole blood flow conditions with high or low shear rates. We determined that pravastatin significantly suppressed platelet activation-dependent procoagulant activity, decreasing P-selectin membrane expression, tissue factor accumulation, and thrombin binding within platelet thrombi generated on a von Willebrand factor-surface under high shear rate conditions. These effects resulted in reductions of intra-thrombus fibrin deposition. These antithrombotic properties of pravastatin, which were comparable to those of atorvastatin, could be abrogated by mevalonate. Our experimental approach revealed a novel mechanism mediating the anti-platelet action of statins. Shear rate-dependent antithrombotic activity may explain the favourable effect of pravastatin on the reduction in cardiovascular events that typically occur in vivo under whole blood flow conditions with high shear rates.