Cardiovascular disease is the main cause of death in Europe and atherosclerosis, a disease of arteries, is the major contributor to this burden. Leucocytes, which are recruited by chemokines, participate in all disease stages: atheromatous plaque formation, instability, and rupture, the latter one being the cause of acute myocardial infarction. My findings suggest that the CXCL5 chemokine may play a role in atherosclerosis. I thus propose to investigate the effects of CXCL5 and its receptor CXCR1 in atherosclerosis. Blockade of the CXCL5/CXCR1 axis will be carried out using both a neutralizing antibody approach (anti-CXCL5) and a chimera mouse model approach (CXCR1 knockout cell transfer), in two mouse models of atherosclerosis, one displaying induced unstable plaques and the other natural plaque ruptures. This will provide insight into the role of CXCL5/CXCR1 axis in atheromatous plaque instability and rupture. Importantly, different types of leucocytes express CXCR1 and the development of a conditional CXCR1 knockout mouse model will provide a better understanding of CXCR1 functions in terms of its spatiotemporal dynamics. Critically, the analysis of human plaques will substantiate these findings in a clinical setting. The findings of this study will define the function of CXCL5/CXCR1 axis in atherosclerosis and offer significant potential for novel therapeutic targets and/or markers for atherosclerosis. The IEF would provide me with the opportunity to enhance my skill base by gaining expertise across a range of disciplines including transgenic mouse development, functional immunological techniques, bioengineering and clinical research. This project involves a collaborative effort across three European countries, offering the potential for an exchange of ideas and the further development of future synergies and interactions. These qualities will be fundamental to establish myself, as an independent scientist in molecular inflammation and cardiovascular research.
Start Date: 01.07.2010 End Date: 30.06.2012 EU Contribution: 161,661 Euro Total Costs: 161,661 Euro Funding Scheme: Intra-European Fellowships (IEF) Scientific Contact: Prof. Dr Michael Bader, mbader(at)mdc-berlin.de