Role of p38 mitogen-activated protein kinase in thrombus formation
Role of p38 mitogen-activated protein kinase in thrombus formation
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DOI：
10.1081/rrs-200040324
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发表时间：
2004-01-01
影响因子：
2.8
通讯作者：
Kasuya, Y
中科院分区：
文献类型：
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作者：
Sakurai, K;Matsuo, Y;Kasuya, Y
本研究旨在阐明 p38 丝裂原激活蛋白激酶 (p38) 在血栓形成中的作用。我们使用 p38alpha 杂合子 (p38alpha+/-) 小鼠，并使用氯化铁 (FeCl3) 诱导的颈动脉损伤作为血栓形成模型。与野生型 (WT) 小鼠相比，p38α+/- 小鼠中由 FeCl3 诱导的血栓闭塞时间延长。从 p38alpha+/- 小鼠制备的血小板显示出对低浓度 U46619（一种血栓素 A 类似物）的聚集反应受损。此外，与 WT 小鼠相比，由 p38alpha+/- 小鼠制备并被 U46619 激活的血小板与纤维蛋白原的结合较差。 FeCl3诱导的WT小鼠组织因子表达和活性均高于p38α+/-小鼠。这些结果表明p38通过调节血小板功能和组织因子活性在血栓形成中发挥重要作用。
The present study was designed to elucidate the role of p38 mitogen-activated protein kinase (p38) in thrombus formation. We used p38alpha heterozygous (p38alpha+/-) mice and used ferric chloride (FeCl3)-induced carotid artery injury as a model of thrombus formation. The time to thrombotic occlusion induced by FeCl3 in p38alpha+/- mice was prolonged compared to that in wild-type (WT) mice. Platelets prepared from p38alpha+/- mice showed impairment of the aggregatory response to a low concentration of U46619, a thromboxane A, analogue. Furthermore, platelets prepared from p38alpha+/- mice and activated by U46619 were poorly bound to fibrinogen compared with those from WT mice. Both the expression and activity of tissue factor induced by FeCl3 in WT mice were higher than those in p38alpha+/- mice. These results suggest that p38 plays an important role in thrombus formation by regulating platelet function and tissue factor activity.