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Inhibition of 5‐hydroxytryptamine 2A receptor prevents occlusive thrombus formation on neointima of the rabbit femoral artery
Author(s) -
NISHIHIRA K.,
YAMASHITA A.,
TANAKA N.,
KAWAMOTO R.,
IMAMURA T.,
YAMAMOTO R.,
ETO T.,
ASADA Y.
Publication year - 2006
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2005.01702.x
Subject(s) - neointima , thrombus , medicine , platelet activation , platelet , vasoconstriction , femoral artery , cardiology , stent , restenosis
Summary. 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‐HT 2A receptor. However, the roles of 5‐HT 2A receptor in occlusive thrombus formation on disrupted plaque remain obscure. Objective: We investigated the role of 5‐HT 2A 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‐HT 2A receptor after a second balloon‐injury were evaluated using sarpogrelate, a selective 5‐HT 2A 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‐HT 2A 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‐HT 2A 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‐HT 2A receptor appears to play a crucial role in occlusive thrombus formation in diseased arteries via platelet aggregation and vasoconstriction. Inhibition of 5‐HT 2A receptor might help reduce the onset of acute coronary events and of acute coronary occlusion after the intervention.