Role of prostacyclin in the cardiovascular response to thromboxane A2
Role of prostacyclin in the cardiovascular response to thromboxane A2
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DOI：
10.1126/science.1068711
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发表时间：
2002-04-19
期刊：
影响因子：
56.9
通讯作者：
FitzGerald, GA
中科院分区：
文献类型：
--
作者：
Cheng, Y;Austin, SC;FitzGerald, GA
血栓烷（Tx）A（2）是一种血管收缩剂和血小板激动剂。阿司匹林通过抑制血小板环氧合酶（考克斯-1）形成TxA（2）来提供心脏保护作用。前列环素（PGI（2））是一种血管扩张剂，抑制血小板功能。在这里，我们发现损伤诱导的血管增殖和血小板活化在PGI（2）受体（IP）遗传缺陷的小鼠中增强，但在TxA（2）受体（TP）遗传缺陷的小鼠中或用TP拮抗剂治疗的小鼠中受到抑制。在两种受体都缺乏的小鼠中，对血管损伤的增强反应被消除。因此，PGI（2）调节体内血小板-血管相互作用，并特别限制对TxA（2）的反应。这种相互作用可能有助于解释与选择性考克斯-2抑制剂相关的不良心血管效应，与阿司匹林和非甾体抗炎药（NSAID）不同，COX-2抑制剂抑制PGI（2），但不抑制TxA（2）。
Thromboxane (Tx) A(2) is a vasoconstrictor and platelet agonist. Aspirin affords cardioprotection through inhibition of TxA(2) formation by platelet cyclooxygenase (COX-1). Prostacyclin (PGI(2)) is a vasodilator that inhibits platelet function. Here we show that injury-induced vascular proliferation and platelet activation are enhanced in mice that are genetically deficient in the PGI(2) receptor (IP) but are depressed in mice genetically deficient in the TxA(2) receptor (TP) or treated with a TP antagonist. The augmented response to vascular injury was abolished in mice deficient in both receptors. Thus, PGI(2) modulates platelet-vascular interactions in vivo and specifically limits the response to TxA(2). This interplay may help explain the adverse cardiovascular effects associated with selective COX-2 inhibitors, which, unlike aspirin and nonsteroidal anti-Inflammatory drugs (NSAIDs), inhibit PGI(2) but not TxA(2).