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 Fields of science medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosis Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2010-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development" Call for proposal FP7-PEOPLE-2010-IOF See other projects for this call Funding Scheme MC-IOF - International Outgoing Fellowships (IOF) Coordinator KATHOLIEKE UNIVERSITEIT LEUVEN EU contribution € 179 390,40 Address OUDE MARKT 13 3000 Leuven Belgium See on map Region Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven Activity type Higher or Secondary Education Establishments Administrative Contact Stijn Delauré (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
