Role of heparanase as a risk factor for arterial thrombosis in Antiphospholipid Antibody Syndrome
| Componente | Categoria |
|---|---|
| Maurizio Sorice | Tutor di riferimento |
In the present study we will investigate the role of heparanase in the pathogenesis of Antiphospholipid Syndrome (APS), implementing a rational drug design approach to discover and develop new drug compounds such as heparanase inhibitors. Antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity. It is well known that in these patients thrombosis may be the result of a hypercoagulable state related to anti-beta2-glycoprotein I (beta2-GPI) antibodies. We recently demonstrated that anti-beta2-GPI antibodies trigger a signal transduction pathway leading to TF expression, the major initiator of the clotting cascade in human platelets, monocytes and endothelial cells.
Thus, this research project is developed in 3 main objectives:
1. Analysis of heparanase activity in sera of APS patients and relationship with clinical features and active arterial thrombosis;
2. Analysis of the role of heparanase in the signal transduction pathway triggered by anti-beta2-GPI antibodies and in the production of tissue factor in coagulation process;
3. Evaluation of the effect of heparanase inhibitors on tissue factor expression and release.
All the compounds will be previously tested for selectivity, efficacy and safety.
Research in this field may contribute to clarify whether pharmacological regulation of heparanase might modify the disease activity, thus disclosing new potential therapeutic targets for APS.