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Sickle Cell transgenic mice demonstrate a pro‐thrombogenic phenotype
Author(s) -
Gavins Felicity n.e.,
Russell Janice,
Granger D Neil
Publication year - 2009
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.23.1_supplement.613.29
Subject(s) - thrombus , microcirculation , genetically modified mouse , coagulation , transgene , thrombosis , immunology , medicine , cell , phenotype , cancer research , pathology , chemistry , biochemistry , gene
In this study we investigated the mechanisms involved in thrombus formation in sickle cell disease (SCD) because SCD patients are more susceptible to thrombotic events, with unknown reason. Thrombosis was induced using the light/dye method in cerebral venules and arterioles of wild‐type (WT:C57Bl/6), sickle cell transgenic (SCD; βs) and WT/βs chimeric (positive control) mice (1). Flow cessation time was recorded. Thrombus formation was reduced by 50% in SCD mice vs. WT in venules and arterioles, but not observed in chimeric mice. The clinical implication of anti‐coagulant therapy was investigated, using Hirudin and anti‐thrombin III (AT3) inhibitor. Hirudin increased thrombus formation in SCD mice, but only in WT venules, suggesting a possible heightened sensitivity in SCD microvasculature. The AT3 inhibitor increased flow cessation in all vessels of WT and SCD mice, implicating the importance of all coagulation pathways. This study further supports the growing evidence for a pro‐inflammatory and pro‐thrombogenic microcirculation in SCD mice, in particular the notion that SCD promotes thrombus formation. Understanding the susceptibility and pathways involved in thrombogenic situations that occur in SCD, it may lead to the identification of potential therapeutic targets in this painful and life‐threatening disease. Supported by the BBSRC 1. Wood, K. et al. AJPHCP. 2004.