AIMS: Oral anticoagulation is considered standard therapy for @entity64 prevention in @entity955 ( @entity955 ). Endocardial activation triggers expression of pro-thrombotic mediators including @entity16963 ( @entity16963 ) and @entity2289 ( @entity2289 ), and contributes to @entity715 formation in the left atrial appendage (LAA) of @entity955 @entity1 . Recently, pleiotropic effects of specific @entity3075 receptor antagonists were demonstrated; however, whether these drugs possess antithrombotic effects on LAA endocardial cells currently remains unknown. METHODS AND RESULTS: LAA were obtained from 14 @entity1 with known @entity955 undergoing elective cardiac surgery including LAA removal at the University Hospital Zurich. LAA endocardial cells were isolated and pre-incubated with @entity3077 (10(-7), 10(-6), 10(-5)M) or @entity1397 active metabolite (CAM) (1.5   *   10(-8), 1.5   *   10(-7), 1.5   *   10(-6) M) before stimulation with @entity5 necrosis factor-alpha ( @entity310 ) (10   ng/mL). Finally, @entity16963 and @entity2289 expression and activity were analysed. @entity3077 , unlike CAM, concentration dependently decreased @entity310 -induced @entity16963 expression and @entity16963 activity in LAA endocardial cells. Further, @entity3077 , but not CAM reduced @entity2289 expression and enzyme activity in @entity310 -stimulated LAA endocardial cells. In contrast, @entity16963 pathway inhibitor (TFPI) remained unaffected by both dugs. CONCLUSION: @entity3077 , but not CAM, reduces expression and activity of @entity16963 and @entity2289 in LAA endocardial cells isolated from @entity1 with @entity955 , indicating possible local antithrombotic effects. Such pleiotropic properties of @entity3077 may contribute to a @entity1031 in @entity1 with @entity955 .

XXXX , but not @entity1397 active metabolite, displays antithrombotic properties in the left atrial endocardium.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity64 :: ('MESH:D020521', 'Disease') :: ['stroke'] @entity2289 :: ('5054', 'Gene') :: ['plasminogen activator inhibitor-1', 'PAI-1'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumour'] @entity1397 :: ('MESH:C055162', 'Chemical') :: ['clopidogrel'] @entity310 :: ('7124', 'Gene') :: ['TNF-a'] @entity3077 :: ('MESH:C503700', 'Chemical') :: ['ticagrelor', 'Ticagrelor'] @entity16963 :: ('2152', 'Gene') :: ['TF', 'tissue factor'] @entity1031 :: ('MESH:D013923', 'Disease') :: ['reduction in thromboembolic complications'] @entity955 :: ('MESH:D001281', 'Disease') :: ['atrial fibrillation', 'AF'] @entity715 :: ('MESH:D013927', 'Disease') :: ['thrombus'] @entity3075 :: ('64805', 'Gene') :: ['P2Y12']
@entity3077 :: (MESH:C503700,Chemical) :: ['Ticagrelor']
