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Increased microparticle procoagulant activity in mice lacking alpha(1,3)‐fucosyltransferase‐IV and –VII
Author(s) -
Wang Huili,
MoralesLevy Maria,
Homeister Jonathon W.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.951.12
Subject(s) - chemistry , microparticle , fucosyltransferase , tissue factor , partial thromboplastin time , prothrombin time , fucosylation , coagulation , platelet , thromboplastin , thromboelastography , endocrinology , medicine , glycan , biochemistry , enzyme , biology , astrobiology , glycoprotein
Fucosylation of selectin ligand glycans by alpha(1,3)‐fucosyltransferases (FucT)‐IV or ‐VII is required for sialyl Lewis x formation and selectin‐binding activity. FucT‐IV(−/−)/FucT‐VII(−/−) mice (DKO) have a 43% decrease in the time to arterial thrombosis due in part to enhanced whole blood platelet aggregation. We evaluated the contribution of the coagulation system to enhanced thrombosis. Fibrinometric determinations of intrinsic and extrinsic pathway activity were not different between WT (n=8) and DKO (n=8) mice [prothrombin time: WT = 12.4±0.3 vs DKO = 12.1±0.4, p=0.11; activated partial thromboplastin time: WT = 29.5±1.9 vs DKO = 28.2±2.6, p=0.28]. Similarly, parameters of the calibrated automated thrombography assay were not different between WT (n=10) and DKO (n=10) mice [lag time: WT = 4.1±1.4 vs DKO = 4.2±0.8, p=0.82; time to peak: WT = 10.4±2.1 vs DKO = 9.4±1.8, p=0.28; peak height: WT = 21.2±6.0 vs DKO = 23.7±4.3, p=0.29; endogenous thrombin potential: WT = 359±123 vs DKO = 336±77, p=0.6]. In contrast, total microparticle procoagulant activity was elevated 3 fold in DKO (n=8) mice compared to WT (n=8) mice [WT = 0.21±0.2 vs DKO = 0.6±0.2, p=0.02], due primarily to microparticle tissue factor‐dependent activity [WT = 0.08±0.1 vs. DKO = 0.23±0.22, p=0.1]. Microparticle tissue factor activity contributes in part to the enhanced thrombosis in DKO mice. Support by AHA FTF Award 0275023N and RO1‐HL090823.