In this project we will investigate the role of ß-amyloid peptide (Aß) and its precursor (APP) in atherosclerosis. Hitherto, APP has only been studied in brain tissue in Alzheimer's disease. A possible source for APP in atherosclerotic plaques are platelets. We will study 1) the localisation and distribution of APP and A? in human atherosclerotic plaques and in a model of atherosclerosis; 2) the association with inducible nitric oxide synthase (iNOS); 3) the influence of cholesterol and lipids on ?-amyloid deposition in models with APP overexpression; 4) the interaction between APP processing and iNOS expression; 5) the effect of Aß on the endothelial cell function of blood vessels. These data could lead to a better understanding of the role of processing of APP, derived from platelets, in the destabilisation and rupture of an atherosclerotic plaque and on the endothelial cell function of blood vessels.