Apolipoprotein E receptor 2 is involved in the thrombotic complications in a murine model of the antiphospholipid syndrome
Copyright policy )Apolipoprotein E receptor 2 is involved in the thrombotic complications in a murine model of the antiphospholipid syndrome
AbstractAntiphospholipid (aPL)/anti-β2 glycoprotein I (anti-β2GPI) antibodies stimulates tissue factor (TF) expression within vasculature and in blood cells, thereby leading to increased thrombosis. Several cellular receptors have been proposed to mediate these effects, but no convincing evidence for the involvement of a specific one has been provided. We investigated the role of Apolipoprotein E receptor 2 (ApoER2′) on the pathogenic effects of a patient-derived polyclonal aPL IgG preparation (IgG-APS), a murine anti-β2GPI monoclonal antibody (E7) and of a constructed dimeric β2GPI I (dimer), which in vitro mimics β2GPI-antibody immune complexes, using an animal model of thrombosis, and ApoER2-deficient (−/−) mice. In wild type mice, IgG-APS, E7 and the dimer increased thrombus formation, carotid artery TF activity as well as peritoneal macrophage TF activity/expression. Those pathogenic effects were significantly reduced in ApoER2 (−/−) mice. In addition, those effects induced by the IgG-APS, by E7 and by the dimer were inhibited by treatment of wild-type mice with soluble binding domain 1 of ApoER2 (sBD1). Altogether these data show that ApoER2 is involved in pathogenesis of antiphospholipids antibodies.
- Utrecht University Netherlands
- University Medical Center Utrecht Netherlands
- The University of Texas System United States
- The University of Texas Medical Branch at Galveston United States
Mice, Knockout, Drug Evaluation, Preclinical, Antibodies, Monoclonal, Thrombosis, Middle Aged, Antiphospholipid Syndrome, Mice, Inbred C57BL, Disease Models, Animal, Mice, beta 2-Glycoprotein I, Immunoglobulin G, Antibodies, Antiphospholipid, Animals, Humans, Antibodies, Phospho-Specific, LDL-Receptor Related Proteins
Mice, Knockout, Drug Evaluation, Preclinical, Antibodies, Monoclonal, Thrombosis, Middle Aged, Antiphospholipid Syndrome, Mice, Inbred C57BL, Disease Models, Animal, Mice, beta 2-Glycoprotein I, Immunoglobulin G, Antibodies, Antiphospholipid, Animals, Humans, Antibodies, Phospho-Specific, LDL-Receptor Related Proteins
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