Inhibition of 5-hydroxytryptamine receptor prevents occlusive thrombus formation on neointima of the rabbit femoral artery.
Inhibition of 5-hydroxytryptamine receptor prevents occlusive thrombus formation on neointima of the rabbit femoral artery.
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发表时间：
2006
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通讯作者：
K. Nishihira;A. Yamashita;N. Tanaka;R. Kawamoto;T. Imamura;R. Yamamoto;T. Eto;Y. Asada
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作者：
K. Nishihira;A. Yamashita;N. Tanaka;R. Kawamoto;T. Imamura;R. Yamamoto;T. Eto;Y. Asada
背景：斑块破裂后血栓的扩散是急性冠状动脉事件和冠状动脉介入治疗后严重并发症的主要原因。5-羟色胺(5-HT)是一种主要由5-HT2a受体介导的有效的血管活性物质和血小板聚集物质。然而，5-HT2a受体在斑块破裂闭塞血栓形成中的作用尚不清楚。目的采用兔反复球囊损伤模型，探讨5-HT2A受体在血栓形成中的作用。方法首次球囊损伤股动脉3周后，观察血管内径、新生内膜生长及5-羟色胺(5-HT)对血管收缩的影响。用选择性5-HT2A受体拮抗剂Sarpogrelate评价血栓的增殖和5-HT2A受体在二次球囊损伤后的作用。结果首次球囊损伤后3周，股动脉出现明显的管腔狭窄，新生内膜表达组织因子和5-HT2A受体。5-羟色胺对狭窄动脉的收缩反应明显减弱。球囊损伤新生内膜，血流量显著减少，促进了闭塞性血栓的形成，该血栓对糖蛋白IIb-IIIa、5-HT2a受体和纤维蛋白免疫反应。静脉注射沙波吉可显著抑制5‘-二磷酸腺苷、凝血酶和胶原诱导的体外血小板聚集以及5-羟色胺诱导的血小板聚集，并显著抑制体内闭塞性血栓的形成。结论5-HT2a受体可能通过血小板聚集和血管收缩在病变动脉闭塞性血栓形成中起重要作用。抑制5-HT2a受体可能有助于减少急性冠状动脉事件的发生和干预后急性冠状动脉闭塞的发生。
BACKGROUND Thrombus propagation on disrupted plaque is a major cause of acute coronary events and serious complication after coronary intervention. 5-Hydroxytryptamine (5-HT) is a potent vasoactive and platelet-aggregating substance that is predominantly mediated by 5-HT2A receptor. However, the roles of 5-HT2A receptor in occlusive thrombus formation on disrupted plaque remain obscure. OBJECTIVE We investigated the role of 5-HT2A receptor in thrombus formation using a rabbit model of repeated balloon-injury. METHODS Three weeks after a first balloon-injury of the femoral arteries, luminal diameter, neointimal growth, and vasoconstriction by 5-HT in vitro were examined. Thrombus propagation and the role of 5-HT2A receptor after a second balloon-injury were evaluated using sarpogrelate, a selective 5-HT2A receptor antagonist. RESULTS Three weeks after the first balloon-injury, luminal stenosis was evident in the femoral arteries, where the neointima expressed tissue factor and 5-HT2A receptor. The hypercontractile response of the stenotic arteries to 5-HT was significantly reduced by sarpogrelate. Balloon-injury of the neointima with substantially reduced blood flow promoted the formation of occlusive thrombus that was immunoreactive against glycoprotein IIb-IIIa, 5-HT2A receptor and fibrin. Intravenous injection of sarpogrelate significantly inhibited ex vivo platelet aggregation induced by adenosine 5'-diphosphate, thrombin and collagen alone as well as with 5-HT, and significantly prevented occlusive thrombus formation in vivo. CONCLUSIONS The 5-HT2A receptor appears to play a crucial role in occlusive thrombus formation in diseased arteries via platelet aggregation and vasoconstriction. Inhibition of 5-HT2A receptor might help reduce the onset of acute coronary events and of acute coronary occlusion after the intervention.