Cheng Yan, Austin Sandra C, Rocca Bianca, Koller Beverly H, Coffman Thomas M, Grosser Tilo, Lawson John A, FitzGerald Garret A
Center for Experimental Therapeutics, 153 Johnson Pavilion, 3620 Hamilton Walk, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6084, USA.
Science. 2002 Apr 19;296(5567):539-41. doi: 10.1126/science.1068711.
Thromboxane (Tx) A2 is a vasoconstrictor and platelet agonist. Aspirin affords cardioprotection through inhibition of TxA2 formation by platelet cyclooxygenase (COX-1). Prostacyclin (PGI2) 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 PGI2 receptor (IP) but are depressed in mice genetically deficient in the TxA2 receptor (TP) or treated with a TP antagonist. The augmented response to vascular injury was abolished in mice deficient in both receptors. Thus, PGI2 modulates platelet-vascular interactions in vivo and specifically limits the response to TxA2. 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 PGI2 but not TxA2.
血栓素（Tx）A2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化酶（COX-1）形成TxA2来提供心脏保护作用。前列环素（PGI2）是一种抑制血小板功能的血管扩张剂。在此我们表明，在基因上缺乏PGI2受体（IP）的小鼠中，损伤诱导的血管增殖和血小板活化增强，但在基因上缺乏TxA2受体（TP）的小鼠或用TP拮抗剂处理的小鼠中则受到抑制。在两种受体均缺乏的小鼠中，对血管损伤的增强反应被消除。因此，PGI2在体内调节血小板与血管的相互作用，并特别限制对TxA2的反应。这种相互作用可能有助于解释与选择性COX-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（NSAIDs）不同，选择性COX-2抑制剂抑制PGI2但不抑制TxA2。
