Identification and targeting of genes in atherosclerosis

The aim of the studies described in this thesis was to assess the relevance of variations in known and novel genes for CVD associated endpoints in order to ultimately identify therapeutic targets for the treatment of atherosclerosis. The type of research is truly translational; it nourishes on the data derived from our outpatient clinics and hospital wards. Despite the vast arsenal of drugs and interventions currently available, residual cardiovascular disease risk remains high. We focused on genetics as a tool for the identification of new targets for therapies. Cardiovascular disease and cholesterol levels are both driven for a large part by genetic factors, of which a majority is still unknown. In analogy to the effective LDL-C lowering therapies, once initiated on the basis of epidemiologic and genetic studies, HDL-C and triglycerides (TG) have emerged as new therapeutic targets. In part I, we studied new genetic variants in relation to HDL and TG levels in families. Next, we moved to therapeutic targets currently in development that are derived from previous genetic studies in part II. Finally, in part III we discuss new potential targets in unknown pathways, identified in rare families with an autosomal pattern of cardiovascular disease in the absence of traditional risk factors