Objective Antiphospholipid syndrome (APS) is an autoimmune disease, characterized by recurrent thrombosis in presence of circulating antiphospholipid antibodies (aPL). aPL activate endothelial cells (ECs) by up-regulating adhesion molecules, IL-6 production and modulating prostaglandin metabolism. Among aPL, anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) have been shown to induce NF-kappaB nuclear translocation leading to a pro-inflammatory endothelial cell phenotype and thereby inducing acute phase proteins, such as serum amyloid A (SAA). SAA is a cytokine, a marker of inflammation and a predictor of cardiovascular disease.SAA has been shown to bind the same receptor used by the anti-inflammatory lipid mediator Lipoxin A4 (LXA4) and elicit opposing pro-inflammatory effects. An association was found between elevated levels of anti-SAA antibodies and aortic stenosis, deep vein thrombosis, and systemic lupus erythematosus. It is largely unclear how SAA may play a role in pro-thrombotic events. The objective of t his proposal is to understand the role of anti-beta2-GPI antibodies and SAA in activating pro-thrombotic inflammatory responses in the endothelium and to determine the inhibitory effects by which LXA4 could counteract these molecular signaling pathways.Our hypothesis states that anti-beta2-GPI antibodies and SAA play relevant roles in the regulation of NF-kappaB, AP-1 and Egr-1. We will use primary ECs and endothelial cell lines to determine the molecular events by which anti-beta2-GPI antibodies and SAA i n presence and absence of LXA4 affect the transcriptional regulation of target genes (such as IL-6, IL-8, tissue factor). We will also determine whether anti-SAA autoantibodies are associated with cardiovascular inflammation in autoimmune diseases. In summary, results from the proposed study have a potential for providing a novel therapeutic approach to treatment of inflammatory events related to cardiovascular manifestations of autoimmune diseases. Fields of science medical and health sciencesclinical medicineangiologyvascular diseasesnatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosisnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicineimmunologyautoimmune diseases Keywords Antiphospholipid syndrome anti anti-inflammation inflammation lipoxins serum amyloid A thrombosis Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG) Call for proposal FP6-2004-MOBILITY-12 See other projects for this call Funding Scheme IRG - Marie Curie actions-International re-integration grants Coordinator UNIVERSITY MEDICAL CENTRE LJUBLJANA DEPARTMENT OF RHEUMATOLOGY Address Zaloska cesta 002 Ljubljana Slovenia See on map Links Website Opens in new window EU contribution € 0,00
