Objective
Based on accumulating clinical-pathological evidence, endothelial cells (EC) are considered to be central to the "injury" model for atheroma formation. Comprehensive goal of this project is to define the earliest molecular and functional response of quiescent, differentiated EC to potentially injurious stimuli, and to search for "natural antagonists" of such response, capable of preventing or reverting the functional consequences of EC injury.
Based on their biological role as a continuous interface between the bloodstream and neighbouring tissues, and on accumulating clinical-pathological evidence, endothelial cells (EC) are considered to be central to the "injury" model for atheroma formation. It is thought that multiple risk factors lead to EC dysfunction, which in turn elicits a series of cellular interactions that culminate in the formation of atherosclerotic lesions. It is the aim of this project to gather several prominent groups in the fields of vascular biology, immunology and inflammation around one major unsolved biological problem, namely the early functional response of quiescent EC to potentially atherogenic stimuli. In an attempt to create a suitable in vitro model for the study of the aforementioned events, major emphasis will be initially placed on defining molecular parameters of EC quiescence, based on comparative in vivo and in vitro analysis of a number of early EC activation/proliferation markers. To this aim, we will create a Centralized Facility for the isolation, culture and characterisation of primary EC from various vascular areas. The Centralized Facility will devise the in vitro models for EC growth and differentiation, produce selected reagents, molecular probes and cDNA constructs and set the standards to be utilised by all participating teams during the investigation. Using a number of functional assays, we will subsequently evaluate the response of quiescent EC cultures to a number of prototypic injurious stimuli involved in the pathogenesis of atheroma formation [unmodified or oxidised lipoproteins, advanced glycation end-products (AGE) and leukocyte adhesion per se]. The analysed functions will include the assessment of trans-EC permeability to macromolecules, the ability of EC to support leukocyte adhesion and chemotaxis, the evaluation of structural and functional changes in molecules responsible for intercellular EC junctions and cytoskeletal organisation, and the acquisition of immunogenic features leading to T lymphocyte activation. mRNA transcripts selectively induced by the described injurious stimuli and possibly related to the observed functional alterations will be searched, cloned and characterised using a PCR-based, differential mRNA screening approach termed "Differential Display RT-PCR". Short- and medium-term consequences of EC exposure to the aforementioned injuries will be evaluated in vivo in two experimental animal models (hamster and mouse) using intravital microscopy. At a later stage in the project, we will search for natural antagonists of EC response to injury, using combined molecular and functional approaches, mainly consisting of subtractive or differential hybridisation techniques followed by expression cloning of the cDNAs whose products interfere with the observed responses to injury.
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.
- natural sciences physical sciences optics microscopy
- medical and health sciences basic medicine immunology
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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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.
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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
20132 MILANO
Italy
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.