Abstract:
:Prasugrel, through its active metabolite, reduces atherothrombosis and its clinical manifestations by inhibiting platelet activation and aggregation. Platelets also contribute to inflammation through interaction with different classes of leukocytes. We investigated whether the inhibitory effect of prasugrel on platelets also counteract inflammatory responses. The effect of prasugrel active metabolite, R-138727, was investigated on platelet P-selectin expression, platelet adhesion to polymorphonuclear leukocytes (PMN) and monocytes (MN) and Mac-1 expression in PMN and MN, in vitro, in human cells. The ex vivo effect of prasugrel administration on P-selectin, thromboxane (TXB)2 formation, platelet-PMN conjugates and Mac-1 expression in PMN triggered by PAR-4 agonist peptide was examined in whole blood from healthy mice as well as from mice in which an acute inflammatory reaction was induced by treatment with endotoxin. The effect of prasugrel on inflammatory markers in endotoxin-treated animals was also tested in vivo. R-138727 inhibited agonist-stimulated expression of platelet P-selectin, platelet-PMN and platelet-MN adhesion and platelet-dependent Mac-1 expression in leukocytes. Addition of aspirin did not modify the inhibitory effect elicited by R-138727. Treatment of mice with prasugrel resulted in a profound inhibition of platelet P-selectin expression, TXB2 production, platelet-PMN adhesion and Mac-1 expression in PMN induced by ex vivo stimulation with PAR-4 agonist peptide of whole blood from healthy or endotoxin-treated mice. Measurement of markers revealed that prasugrel reduced TXB2 and tumour necrosis factor-α synthesis and increased nitric oxide metabolites in endotoxin-treated mice in vivo. In conclusion, prasugrel reduces platelet interactions with PMN and MN. Through these effects prasugrel may curb platelet-mediated inflammatory responses.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Totani L,Dell'Elba G,Martelli N,Di Santo A,Piccoli A,Amore C,Evangelista Vdoi
10.1160/TH11-12-0867subject
Has Abstractpub_date
2012-06-01 00:00:00pages
1130-40issue
6eissn
0340-6245issn
2567-689Xpii
11-12-0867journal_volume
107pub_type
杂志文章abstract::We have identified a patient with a dysfunctional prothrombin that we have designated Prothrombin Frankfurt. The proband was characterized by a prothrombin activity level of 13% and 20% compared to normal controls using two different assays with a normal prothrombin antigen level of 91% of normal controls. The genetic...
journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
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更新日期:1995-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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abstract::In the last decades, substantial progress has been made in understanding the relationship between lipid disorders and prevention of cardiac ischemic disease. Statins competitively inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol biosynthesis. Statins have long been t...
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
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doi:
更新日期:2009-05-01 00:00:00
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journal_title:Thrombosis and haemostasis
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pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
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journal_title:Thrombosis and haemostasis
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doi:10.1160/TH07-08-0484
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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