Effect of serotonin, thromboxane A2, and specific receptor antagonists on vascular smooth muscle cell proliferation.
Effect of serotonin, thromboxane A2, and specific receptor antagonists on vascular smooth muscle cell proliferation.
复制标题
血清素、血栓素 A2 和特异性受体拮抗剂对血管平滑肌细胞增殖的影响。
DOI：
10.1161/01.cir.96.7.2280
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发表时间：
1997
期刊：
影响因子：
37.8
通讯作者：
Benedict,CR
中科院分区：
文献类型：
--
作者：
Pakala,R;Willerson,JT;Benedict,CR
背景冠状动脉再狭窄是限制冠状动脉成形术长期疗效的主要并发症。活化的中膜平滑肌细胞（SMCs）的迁移和增殖被认为是这一过程中的重要机制。因为在血管损伤部位，聚集的血小板释放5-羟色胺（5-HT）和血栓烷A2（TXA 2），方法和结果在无血清培养液中，用[~ 3 H]法检测5-HT和TXA_2单独或联合应用对犬主动脉平滑肌细胞的促增殖作用。胸苷掺入DNA和细胞计数。5-HT在100 nmol/L时可诱导SMC增殖，而TXA 2（U46619，一种稳定的TXA 2模拟物）在100 nmol/L时可诱导SMC增殖。当这两种介质加在一起时，即使在阈下浓度下，也存在诱导SMC增殖的协同作用。5-HT 2受体拮抗剂LY 281067可阻断5-HT的促有丝分裂作用及其与TXA 2的协同作用，而不影响TXA 2的作用。同样，血栓素A2合成酶抑制剂/受体拮抗剂瑞多格雷消除了血栓素A2的促有丝分裂作用以及5-HT与血栓素A2之间的相互作用，而不影响对5-HT的反应。当LY 281067和ridogrel联合使用时，它们可消除5-HT和TXA 2的促有丝分裂作用。结论在血管损伤部位，血小板诱导的SMC增殖也可能受到非肽类生长介质的调节。5-HT 2受体拮抗剂和TXA 2合酶抑制剂/受体的组合可用于减弱血管成形术后的再狭窄。
BackgroundRestenosis is a major complication that limits the long-term efficacy of coronary angioplasty. Migration and proliferation of activated medial smooth muscle cells (SMCs) is considered an important mechanism in this process. Because at sites of vascular injury, aggregating platelets release both serotonin (5-HT) and thromboxane A2(TXA2), we examined whether 5-HT and TXA2can induce SMC proliferation and whether there is synergistic interaction between these two mediators.Methods and ResultsThe mitogenic effects of 5-HT and TXA2either alone or in combination was examined in serum-free medium on canine aortic SMCs by [3H]thymidine incorporation into DNA and by cell counting. 5-HT induced SMC proliferation at a concentration of 100 nmol/L, whereas the effect of TXA2(U46619, a stable TXA2mimetic) on inducing proliferation of SMCs was observed at a concentration of 100 nmol/L. When these two mediators were added together, there was a synergistic interaction on inducing SMC proliferation even at subthreshold concentrations. The mitogenic effect of 5-HT and its synergistic interaction with TXA2on SMC proliferation was abolished by a 5-HT2receptor antagonist, LY281067, without affecting the contribution of TXA2. Similarly, the TXA2synthase inhibitor/receptor antagonist ridogrel abolished the mitogenic effect of TXA2and the interaction between 5-HT and TXA2without affecting the response to 5-HT. When LY281067 and ridogrel were used together, they abolished the mitogenic effects of 5-HT and TXA2.ConclusionsAt sites of vascular injury, platelet-induced SMC proliferation may also be modulated by nonpeptide growth mediators. A combination of a 5-HT2receptor antagonist and TXA2synthase inhibitor/receptor may be useful for attenuation of restenosis after angioplasty.