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| Content Provider | PubMed Central |
|---|---|
| Author | Kolyada, Alexey Alfredo, De Biasio Natalia, Beglova |
| Copyright Year | 2013 |
| Abstract | Antiphospholipid syndrome (APS) is an autoimmune disease with clinical manifestations of thrombosis and pregnancy complications. Beta2-glycoprotein I (β2GPI) is the major antigen for the APS-related antibodies. Heparin, low molecular weight heparin and the synthetic pentasaccharide fondaparinux are commonly used for prophylaxis and treatment of thrombosis in patients with antiphospholipid syndrome. These antithrombotic drugs bind and activate antithrombin III to inactivate blood clotting proteases. Heparin and heparin derivatives might have a direct beneficial effect in APS via binding to β2GPI and interfering with prothrombotic properties of β2GPI/antibody complexes. We compared fondaparinux to heparin regarding its ability to bind β2GPI and inhibit the binding of β2GPI/antibody complexes to negatively charged phospholipids and endothelial cells. Although heparin and fondaparinux bind β2GPI at therapeutically relevant doses, neither fondaparinux nor heparin was efficient in inhibition of the binding of β2GPI/antibody complexes to negatively charged phospholipids and endothelial cells. Our studies suggest that these drugs do not act on pathological properties of β2GPI/antibody complexes, emphasizing the need for a new treatment specific for β2GPI-related thrombosis in APS. We observed that the binding interface of fondaparinux on β2GPI does not include the lysine residues known to be critical for binding of heparin. The docking model of the β2GPI complex with fondaparinux is in agreement with multiple experimental observations. |
| Related Links | http://dx.doi.org/10.1016/j.bbapap.2013.06.009 |
| Ending Page | 2088 |
| Page Count | 9 |
| Starting Page | 2080 |
| File Format | |
| ISSN | 00063002 |
| Journal | Biochimica et biophysica acta |
| Issue Number | 10 |
| Volume Number | 1834 |
| Language | English |
| Publisher Date | 2013-10-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
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