Role of heparanase in Antiphospholipid Antibody Syndrome
| Componente | Categoria |
|---|---|
| Fulvia Ceccarelli | Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca |
The antiphospholipid syndrome is characterized by the presence of anti-ß2-GPI antibodies that induce the activation of a signaling pathway leading to the expression of Tissue factor (TF), the major initiator of the clotting cascade in human platelets, monocytes and endothelial cells. Heparanase is an endo-beta-D-glucuronidase capable of cleaving heparan sulfate side chains at a low pH. Recent papers have shown that heparanase is directly involved in the activation of the coagulation system. Heparanase was demonstrated to interact with TF and enhance the generation of factor Xa.
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 symmetrical 2-aminophenyl-benzazolyl-5-acetate derivative (RDS3337), able to inhibit Heparanase activity.
Thus, this research project is developed in 3 main objectives:
1. Analysis of the role of heparanase in the signal transduction pathway triggered by anti-beta2-GPI antibodies;
2. 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;
3. Analysis of heparanase activity in plasma of APS patients and relationship with clinical features and active arterial thrombosis.
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.