Objective
Atherosclerosis is the underlying process leading to the occurrence of cardiovascular diseases that accounts for one-third the world’s mortality. Although multifactorial the pathogenesis of atherosclerosis is triggered to a large extent by elevated plasma cholesterol levels, and by the oxidation of low density lipoprotein (LDL). The central hypothesis of this proposal is that proteins containing Fe protoporphyrin IX (heme) or free heme itself might act as central mechanism via which LDL is oxidized as to become atherogenic.
The vast majority of heme is inside red blood cells (RBC) as the prosthetic group of hemoglobin (Hb). Under homeostasis a small percentage of RBCs lyses intravascularly, resulting presence of cell-free Hb in plasma. Several defence mechanisms evolved to cope with the deleterious effects of cell-free Hb, as well as those of heme itself. Plasma cell-free Hb is bound by haptoglobin (Hp), whereas heme binds to hemopexin (Hx). The formed Hb-Hp and Hb-Hx complexes are cleared from circulation by hemophagocytic macrophages and the heme is degraded by heme-oxygenase-1 (HO-1). This control mechanism prevents the accumulation of cell-free Hb or free heme in plasma while allowing iron recycling. The impairment of this control mechanism leads to severe oxidative stress-mediated pathologies, e.g. Hp-/- as well as Hx-/- mice develop severe renal damage in response to hemolysis, suggesting that this mechanism plays a central role in preventing the pro-oxidant effects of cell-free Hb or heme.
Previous work from the applicant and others have demonstrated that LDL can bind free heme with high affinity with kinetics that are faster than those of Hx and can cause LDL oxidation. It is likely therefore that under conditions in which the plasma concentration of LDL and/or cell-free Hb or heme levels become elevated, the production of heme-LDL complexes would be more prevalent contributing in a critical manner to the development of atherosclerosis.
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 chemical sciences electrochemistry electrolysis
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules proteins
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2010-RG
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Funding Scheme
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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
4032 Debrecen
Hungary
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.