Objective Coronary artery disease, the primary cause of death in the western world, is induced by an acute cessation of the blood flow due to the formation of an occluded thrombus or blood clotin or nearby an unstable atherosclerotic lesion. Whether or not thrombotic complications will ensue from plaque rupture is strongly dependent on the presence of procoagulant molecules within the plaque. Interference with their activity thus represents a promising approach to influence the initiation and progression of the disease. The general goal of the project is:- to inhibit expression and activity of procoagulant proteins by delivering specific enzymes and,- to modulate the activity of transcription factors regulating these proteins.Modulation will be effected by atherosclerotic plaque-directed adenoviral gene transfer, bone marrow transplantation from corresponding transgenics and administration of therapeutic inhibitors in an advanced mouse model of accelerated atherosclerosis. The effect on the plaque size and morphology as well as on its lipid content and thrombotic nature will be determined. We anticipate that the results will lead to new therapeutic entries for reducing the thrombogenicity of atherosclerotic plaques and thus preventing thrombotic complications. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosisnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesclinical medicinetransplantationnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Keywords adenovirus atherosclerosis bone marrow transplantation lentivirus Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2002-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator UNIVERSITEIT LEIDEN EU contribution No data Address Rapenburg 70 LEIDEN Netherlands See on map Total cost No data
