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Modulation of Endothelial ADAMTS‐13 Expression and Activity
Author(s) -
Wilson Emily
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.lb42
Subject(s) - adamts , von willebrand factor , thrombospondin , thrombotic thrombocytopenic purpura , umbilical vein , adamts13 , disintegrin , metalloproteinase , chemistry , tumor necrosis factor alpha , platelet , microbiology and biotechnology , immunology , matrix metalloproteinase , biology , in vitro , biochemistry
ADAMTS‐13 (a member of the A Disintegrin and Metalloprotease with Thrombospondin type motif family) functions to cleave unusually large (UL) of von Willebrand factor (VWF) that are secreted from activated endothelial cells. Cleavage of VWF by ADAMTS‐13 converts the UL forms to smaller forms that are hemostatically but not pro‐thrombotic. ADAMTS‐13 deficiency is associated with systemic thrombosis , typically thrombotic thrombocytopenic purpura (TTP).. Recent studies showed that endothelial cells expressed ADAMTS‐13 constitutively and that this may also be an important source of ADAMTS‐13. We hypothesized that local regulation of expression levels and activity of ADAMTS‐13 may be an important determinant in platelet adhesion in various other diseases including atherosclerosis, deep vein thrombosis and shock. Specifically, we hypothesized that expression and or activity of ADAMTS‐13 might be modulated in a shear stress‐dependent manner. NO production is associated with regions of high shear stress and inhibits platelet adhesion and thrombosis. We treated human umbilical vein endothelial cells (HUVECs) an NO resulting in a 30‐40% increase in both mRNA and protein Hoever, the activity of secreted ADAMTS‐13 increased by 3 fold as determined using a fluorescent peptide substrate. Treatment with Tumor necrosis factor‐alpha (TNF) casused a marked decrease in protein levels (50%) and activity (45%). These results support the hypothesis that local changes in ADAMTS‐13 expression and activity may contribute to regions of the vasculature that are either pro‐ or anti‐thrombotic and thus may contribute localization of specific vascular diseases. This work was supported by the Mary R. Gibson Foundation.