Inhibition of 5‐hydroxytryptamine2Areceptor prevents occlusive thrombus formation on neointima of the rabbit femoral artery

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‐HT2Areceptor. However, the roles of 5‐HT2Areceptor in occlusive thrombus formation on disrupted plaque remain obscure. Objective: We investigated the role of 5‐HT2Areceptor 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 vitrowere examined. Thrombus propagation and the role of 5‐HT2Areceptor after a second balloon‐injury were evaluated using sarpogrelate, a selective 5‐HT2Areceptor 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‐HT2Areceptor. 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‐HT2Areceptor and fibrin. Intravenous injection of sarpogrelate significantly inhibited ex vivoplatelet 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‐HT2Areceptor appears to play a crucial role in occlusive thrombus formation in diseased arteries via platelet aggregation and vasoconstriction. Inhibition of 5‐HT2Areceptor might help reduce the onset of acute coronary events and of acute coronary occlusion after the intervention.