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Thrombosis and platelet aggregation is enhanced in mice deficient in alpha(1,3)‐fucosyltransferases‐IV and ‐VII
Author(s) -
Homeister Jonathon W.,
Bodary Peter F.,
Machlus Kellie R.
Publication year - 2008
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.22.1_supplement.1118.2
Subject(s) - chemistry , platelet , medicine , partial thromboplastin time , platelet activation , endocrinology , inflammation , thrombosis , immunology
P‐selectin is a link between inflammation and venous or microvascular thrombosis. Selectin‐mediated leukocyte/endothelial interactions require ligands that contain sialyl Lewis x, which is absent in mice deficient in alpha(1,3)‐fucosyltransferases (FucT)‐IV and ‐VII. We tested whether mice deficient in the FucTs had the predicted anti‐thrombotic phenotype in a photochemical‐induced injury model of carotid artery thrombosis. Surprisingly, the time to thrombosis was decreased in FucT‐IV(−/−)/FucT‐VII(−/−) mice [16.5±5.1 min, n=4, vs WT=36.2±2.6 min, n=8; p≤0.05]. The prothrombotic phenotype was not accounted for by alterations of the prothrombin time [FucT‐IV(−/−)/FucT‐VII(−/−)=12.2±0.4 sec, n=8 vs WT=12.4±0.3 sec, n=8; p≥0.05], activated partial thromboplastin time [FucT‐IV(−/−)/FucT‐VII(−/−)=28.2±2.6 sec, n=8 vs WT=29.5±1.9 sec, n=8; p≥0.05], or platelet count [FucT‐IV(−/−)/FucT‐VII(−/−)=775±121 × 10 3 /ul, n=9 vs WT=721±107 × 10 3 /ul, n=9; p≥0.05]. In contrast, collagen‐stimulated whole blood platelet aggregation in FucT‐deficient mice had a shorter lag time [FucT‐IV(−/−)/FucT‐VII(−/−)=68±5.8 sec, n=5 vs WT=90±5.7 sec, n=5; p≤0.05], and a faster rate [FucT‐IV(−/−)/FucT‐VII(−/−)=16.2±1.5 sec −1 , n=5 vs WT=13.4±1.7 sec −1 , n=5; p≤0.05]. FucT‐deficient mice have a prothrombotic phenotype that is associated with enhanced platelet aggregation. Support by AHA FTF Award 0275023N.