Objective
Three clear objectives, with defined milestones, are at the heart of this project:
Identification of adhesion molecules implicated in initiating and perpetuating atherosclerotic lesions. An important aspect of this work will be to compare data from transgenic Apo(e) mouse used in different models (diets and/or heterotypic cardiac transplantation), to pig atherosclerosis and to results observed in human spontaneous or transplantation associated coronary artery disease. Coronary endothelial or smooth muscle cDNA libraries, in a panning technique, will be used to isolate and sequence the cDNA clones of new adhesion molecules or their ligands
Testing the role of adhesion molecules in atherosclerotic lesions (P-selectin and ICAM-1 are lead candidates) by using Apo(e) transgenic animals lacking P-selectin and/or ICAM-1 expression (double or triple knock outs). Loss of these adhesion molecule genes, in transgenic animals, will also be evaluated in heterotypic cardiac transplantation. The role of different adhesion molecules and/or platelet activating factor (PAF) will be tested in adhesion or coculture chamber assays to look at the binding and extravasation of monocytes and T Iymphocytes.
Validation of the role played by adhesion molecules in atherosclerotic lesions will be evaluated in different Apo(e) transgenic animal models (on diets and/or heterotypic cardiac transplantation) with linear or cyclic peptides. Such validation of the role played by adhesion molecules will also be performed in the porcine model of vascular reperfusion injury and restenotic injury using blocking monoclonal antibodies or peptides.
Complications following atherosclerotic plaque formation are responsible for about half of total death in the European Union. The cost of such disease to member states is rapidly increasing with the rise of wealth and standard of living. Generation of new drugs to prevent plaque initiation, perpetuation or even rupture could have a tremendous impact on public health and in promoting European Union pharmaceutical industry to the forefront of the economic and industrial competition for what would be a global market. The mechanisms allowing the initiation, progression and rupture of atherosclerotic plaques, in arteries occlusion, remains to be identified. Moreover, very little is known on transplant associated coronary artery disease which is the most serious long term complication and is a possible limitation to the long term success of cardiac transplant programmes. However, increasing evidence shows that activated vascular endothelial cells, occurring as a result of various possible insults, will upregulate and/or express adhesion molecules that will allow the rolling, adhesion and extravasation of monocytes / macrophages and a subpopulation of T lymphocytes to subintimal areas. The initiation and perpetuation of atherosclerotic lesions appear to be mediated by these vascular endothelial adhesion molecules. This study will set up a multidisciplinary network of European Union laboratories with the aim of developing new concepts of adhesion blockade to a stage where therapy might be attempted. The multidisciplinary structure of this project, its cutting edge technology, and the experience of its network in adhesion molecules and/or in atherosclerosis gives it a clear lead in reaching its objectives in the generation of new compounds to be used in drug development.
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 basic medicine pharmacology and pharmacy drug discovery
- medical and health sciences health sciences public health
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- medical and health sciences health sciences nutrition
- medical and health sciences clinical medicine transplantation
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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.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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.
Coordinator
69372 Fac. Lyon
France
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.