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 (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine angiology vascular diseases
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine immunology autoimmune diseases
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2004-MOBILITY-12
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
IRG - Marie Curie actions-International re-integration grants
Coordinator
LJUBLJANA
Slovenia
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.