Platelet-mediated Tissue Factor Expression On Leukocytes In Acute Coronary Syndromes And The Inhibitory Effects Of Clopidogrel

Objective:Upon plaque rupture, platelet adhesion, activation and aggregation, and coagulation activation by tissue factor, leading to intracoronary thrombosis, are fundamental mechanisms of acute coronary syndromes (ACS). However, it is not well known whether platelet-activation affects leukocyte tissue factor expression which could play important role in pathophysiology of ACS. This study was designed to explore the effects of platelet-activation on leukocyte tissue factor expressions, and inhibitory effects of clopidogrel on tissue factor expression in acute coronary syndromes.Method:We enrolled 30 consecutive patients with ACS,20 patients with stable angina (SA) and 20 normal volunteers. Isolated plasma samples, containing with or without platelets and platelet release products (PRPS), were then incubated with human monocyte cell line (THP-1), while TRAP (thrombin receptor agonist peptide) and PMA were added as agonists. Six hours after incubation, flowcytometry analyses were performed in every sample to detect the expression of tissue factor. Flowcytometry analyses were also performed in whole blood to detect the expression of tissue factor on monocytes and neutrophils (PMN).Results:In isolated plasma samples from either SA or normal volunteers, TRAP, PMA or PRPS all significantly up-regulated the expression of tissue factor on THP-1 (all P<0.01). Compared to SA or normal volunteers, tissue factor expressions on THP-1 were significantly increased in all plasma samples from ACS patients, including PPP (platelet poor plasma), PRP (platelet rich plasma) with or without TRAP or PMA, or PRPS. Interestingly, after administration of clopidogrel in patients with ACS, tissue factor expressions on THP-1 were significantly reduced by 23% in PPP, by 21% in PRP, by 32% in PRP with TRAP, by 29% in PRP with PMA, or by 33% in PRPS (all P＜0.01).In whole blood samples from ACS, TRAP and PMA significantly up-regulated the expressions of tissue factor on monocytes or neutrophils (all P<0.01). Compared to patients with SA or normal volunteers, tissue factor expressions on monocytes or neutrophils in patients with ACS were all significantly increased in whole blood samples with no agonists, with TRAP or with PMA (all P<0.01). However, after administration of clopidogrel in patients with ACS, tissue factor expressions on monocytes were significantly reduced by 33% in whole blood samples with no agonists, by 41% with TRAP and by 29% with PMA(all P＜0.05), and tissue factor expressions on neutruphols reduced by 35%, by 43%, and by 37%, respectively (all P＜0.01).Conclusion:①Activated platelets and platelet release products up-regulated the expression of tissue factor on leukocytes during acute coronary syndromes.②Clopidogrel inhibited leukocyte tissue factor expressions in patients with acute coronary syndrome.