A DIMER OF B2GLYCOPROTEIN I (B2GPI) UPREGULATES TISSUE FACTOR (TF) AND IS THROMBOGENIC IN VIVO

Abstract number: P-W-459

Romay-Penabad¹ Z., Urbanus² R.T., Pennings² M.T., Montiel-Manzano¹ G., DeGroot² P., Pierangeli¹ S.S.

¹¹Medicine-Rheumatology, University of Texas Medical Branch, Galveston, United States ²²Medicine, Utrecht University, Utrecht, Netherlands

How-to-cite Romay-Penabad Z, Urbanus RT, Pennings MT, Montiel-Manzano G, DeGroot P, Pierangeli SS. A DIMER OF B2GLYCOPROTEIN I (B2GPI) UPREGULATES TISSUE FACTOR (TF) AND IS THROMBOGENIC IN VIVO. J Thromb Haemost 2007; 5 Supplement 2: P-W-459

Abstract

Introduction: It has been shown that endothelial cell (EC) activation and tissue factor (TF) upregulation in EC and monocytes by anti- b₂glycoprotein I (anti-b₂GPI) antibodies leads to a prothrombotic state. In previous studies, dimers of b₂GPI were shown to mimic the effects of b₂GPI-anti- b₂GPI complexes in that they increased platelet adhesion to collagen. Here we examined the effects of a dimeric form of b₂GPI on thrombosis and TF activity in vivo in mice.

Methods: We treated CD1 mice with 50 mg/mL (i.p) recombinant dimeric b₂GPI or with recombinant monomeric b₂GPI twice at 0 and 48 hours later. The size of an induced thrombus in the femoral vein of the mice was examined as described elsewhere. TF activity was determined using a chromogenic assay in homogenates of carotid arteries, and in peritoneal cells of mice

Results: In vivo, b₂GPI dimer increased significantly the size of the induced thrombi when compared to mice treated with control protein. Treatment of the mice with the b₂GPI dimer also induced significantly increased TF function in peritoneal cells and in homogenates of carotid arteries (Table).

Table:

Treatment	Thrombus size (mean SD, mm<SU	TF in carotid artery (pM/mg protein)	TF in macrophages (pM/mg protein)
Dimer	51873801	312	130
Control Peptide	552	238	42

Conclusions: The data show that a dimeric form of b₂GPI mimics the effect of anti-b₂GPI antibodies in vivo and causes TF upregulation that may lead to thrombosis. Thus when b₂GPI is dimerised, it can induce thrombosis in mice independently of the presence of antibodies. These findings may be important in understanding the pathogenic mechanisms of thrombosis in Antiphospholipid Syndrome (APS).

To cite this abstract use the following format:

Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number

Session Details

Date:	01/08/2007
Time:	00:00-00:00
Session name:	XXIst ISTH Congress
Subject:
Location:	Oxford, UK
Presentation type:
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