Pathomechanisms of atherosclerosis and its biomarkers

There is clearly an urgent need for representative animal models in the investigation of atherosclerotic plaque rupture. The primary aim of this study is therefore to generate an animal model which will further the understanding of the mechanism involved in the process of plaque rupture and aid in the development of new therapeutic agents (Chapter 2). The second aim of this study is to develop a non-invasive diagnostic tool for atherosclerosis. We hypothesized that coronary artery disease is reflected in a specific urine polypeptide pattern that originates from proteins present in atherosclerotic plaque (Chapter 4). Thirdly, ApoE-deficient mice provide a controllable pattern of atherosclerosis in experimental conditions. We would like to apply urine proteomic analysis to identify novel biomarkers of atherosclerotic disease (Chapter 3). Fourthly, it is well-known that CRP is associated with cardiovascular risks. Chapter 5 will highlight the divergent effect of monomeric CRP in comparison to pentameric CRP on atherosclerosis. Overall, this thesis will focus on the following objectives: Chapter 2: Creation of a mouse model reflecting human vulnerable plaque rupture (Paper submitted). Chapter 3: Urine Proteome analysis reflects atherosclerotic disease in an ApoE-/- mouse model and allows the discovery of new biomarkers and mediators of atherosclerosis (Paper submitted). Chapter 4: Evaluation of urine proteome pattern analysis for its potential to reflect coronary artery atherosclerosis in symptomatic patients (Paper published). Chapter 5: Dissociation of pentameric to monomeric C-reactive protein on activated platelets localizes inflammation to atherosclerotic plaques (Paper published).