Objective
Cardiovascular diseases (CVDs) are the leading cause of death throughout the world. Elevated Low Density Lipoprotein (LDL) is a well-known cardiovascular risk factor and endothelial (ECs)-lipoprotein (LIPs) interactions underlie the initiation and progression of atherogenesis, thrombosis and other CVDs.
The endothelium is a monolayer of cells that segregates the vascular contents from adjacent tissues. In spite of being continually exposed to LIPs, ECs were long thought of as inert barriers, through which lipids are exchanged between plasma and surrounding tissues. In contrast to this view, recent work from my laboratory has uncovered a deleterious role of ApoB-LIPs as direct inhibitors of angiogenesis in the developing embryo. These findings present only the tip of the iceberg, and the underlying cellular and molecular mechanisms are largely unknown. In this proposal, we will tackle this question by undertaking three independent but complementary approaches, aimed at characterizing LIP-EC interactions at a different level: cellular, molecular or pathological. We will explore these facets in zebrafish and mammals, utilizing live imaging, sophisticated lipidomic and biochemical analyses, as well as tumor xenografts and genetic mutants. An important and unique aspect of our approach is the focus on in vivo dynamics, in contrast to the extensive body of literature on LIP effects on cultured ECs. When completed this proposal will have shed light on a little explored, but critical aspect in the etiology of CVDs. Furthermore it will provide answers to important unresolved questions: What are the signaling pathways activated in ECs upon LIP binding? How are LIPs transported within ECs? Does ApoB possess additional functions beyond that of cholesterol carrier? Can high LIPs levels inhibit tumor angiogenesis and metastasis? In a broader sense, a deeper understanding of the effects of LIPs on ECs will be valuable for identifying new targets for therapeutic intervention.
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 clinical medicine angiology vascular diseases
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences clinical medicine cardiology cardiovascular diseases
- natural sciences biological sciences zoology mammalogy
- medical and health sciences clinical medicine embryology
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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-2013-StG
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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
7610001 Rehovot
Israel
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.