Antiplatelet Therapy: Targeting the TxA2 Pathway
Antiplatelet Therapy: Targeting the TxA2 Pathway
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DOI：
10.1007/s12265-013-9529-1
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发表时间：
2014-02-01
影响因子：
3.4
通讯作者：
Reny, J. -L.
中科院分区：
文献类型：
--
作者：
Fontana, P.;Zufferey, A.;Reny, J. -L.
血栓素（Tx）A（2）通路是初始血小板活化过程放大的主要贡献者。TxA（2）通过血栓素前列腺素类（TP）受体介导其作用，TP受体不仅在血小板中表达，而且在内皮细胞、巨噬细胞和单核细胞中表达，因此有助于动脉粥样硬化病变的发展。因此，TxA（2）通路是治疗心血管疾病的主要靶点。阿司匹林--最广泛使用的抗血小板药物--在抑制血小板源性TxA（2）合成方面非常有效。然而，阿司匹林的作用可以被几种其他可溶性激动剂如异前列烷克服，异前列烷是优先在糖尿病中产生的TP受体的阿司匹林不敏感的配体。已经开发了对Tx合酶具有抑制作用或对TP具有拮抗作用的其他药物，希望提供对TxA（2）途径的更好、更完全的抑制。
The thromboxane (Tx) A(2) pathway is a major contributor to the amplification of the initial platelet activation process. TxA(2) mediates its effect through the thromboxane prostanoid (TP) receptor that is expressed not only in platelets, but also in endothelial cells, macrophages, and monocytes, and thus contributes to the development of atherosclerotic lesions. The TxA(2) pathway is therefore a major target in the treatment of cardiovascular disease. Aspirin-the most widely used antiplatelet drug-is very effective at inhibiting platelet-derived TxA(2) synthesis. However, aspirin's effects can be overcome by several other soluble agonists such as isoprostanes, which are aspirin-insensitive ligands of the TP receptor that are preferentially produced in diabetes mellitus. Other drugs, with either inhibitory effects on Tx synthase or antagonist effects on TP, have been developed with the hope of providing a better, more complete inhibition of the TxA(2) pathway.