Objective
Atherosclerosis is a chronic inflammatory disease of the arterial wall with (auto)immune component, initiated in response to modified (phospho)lipids. Despite important advances in our understanding of the inflammatory response in atherosclerosis, the critical pathways responsible for the breakdown of immune tolerance to lipoproteins and other self-antigens remain largely unknown. An important feature of ruptured/thrombosed atherosclerotic lesions is the accumulation of apoptotic, and secondary necrotic, lipid-laden macrophages and smooth muscle cells due to defective efferocytosis (clearance of apoptotic cells). This leads to the formation of a large ‘necrotic’ lipid core, associated with enhanced vascular inflammation. Interestingly, defective efferocytosis has been associated with the development of autoimmunity, and patients with systemic lupus erythematosus who show increased accumulation of apoptotic material are at very high risk of accelerated atherosclerosis and myocardial infarction. We hypothesize that accumulation of apoptotic/secondary necrotic cells due to defective efferocytosis, together with modified lipids, activate critical immuno-inflammatory pathways in macrophages and B cells, and break immune tolerance in atherosclerosis and post-myocardial infarction. This is consistent with the critical role played by defective efferocytosis and macrophage activation in atherosclerotic lesion progression, and with our recent unsuspected data showing a critical role for B cell activation in driving lesion development in several models of atherosclerosis. We also propose that interactions between macrophages and B cells are essential for the perpetuation of the pathogenic immuno-inflammatory response in cardiovascular disease. Finally, we will harness this knowledge for a better identification of patients at risk of cardiovascular complications, and will target these pathways to limit the progression and complications of cardiovascular disease.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences health sciences inflammatory diseases
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules lipids
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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.
ERC-2011-StG_20101109
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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.
Host institution
CB2 1TN Cambridge
United Kingdom
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.