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Content archived on 2024-05-28

Macrophage Proteoglycans in Atherosclerosis

Objective

Cardiovascular diseases (CVD) are the leading cause of death in Western societies. CVD-related deaths are primarily caused by complications of atherosclerosis, a disease initiated via focal infiltration and retention of lipoproteins in the subendothelial matrix of arteries due to a combination of aggregation and interaction with proteoglycans produced by the arteries. Little is known about the in vivo contribution of macrophage-derived and -associated proteoglycans during atherosclerosis development and progression. Considering this dearth of knowledge we will address two objectives: First, we want to determine the in vivo impact of reduced sulfation of macrophage proteoglycans on atherosclerosis using conditional mouse models lacking macrophage-specific Ndst1 functionality on an LDLR-deficient background. Atherosclerotic lesion quantity and quality will be analyzed in conjunction with macrophage lesion infiltration and lesion apoptosis and efferocytosis. Secondly, we want to evaluate the importance of proteoglycans for macrophage foam cell conversion, another key event in atherogenesis. Using macrophage cell cultures from wild-type or mutant mice we want to determine the importance of biosynthetic genes involved and the array of proteoglycans expressed before and after conversion. In addition the cells will be used to identify a specific proteoglycan important for conversion which will be consequently evaluated for its impact on atherosclerosis in vivo. During his mobility, the applicant will receive didactic (glycobiology, management, intellectual property, grants) and hands-on (MS, macrophage cultures, qPCR, shRNA, flow assay) training as well as network opportunities which will be implemented in the European return institution. Altogether, the generated data should add to our understanding of macrophage proteoglycans and their importance for CVD and provide the opportunity for identifying drug targets and for transfer of US collaborations and know-how to the EU

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2010-IOF
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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.

MC-IOF - International Outgoing Fellowships (IOF)

Coordinator

KATHOLIEKE UNIVERSITEIT LEUVEN
EU contribution
€ 179 390,40
Address
OUDE MARKT 13
3000 Leuven
Belgium

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Region
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

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