Cardiovascular disease (CVD) is a major cause of mortality and morbidity in the Western world. CVD is mainly caused by atherosclerosis, for which dyslipidemia, characterized by high a plasma level... Show moreCardiovascular disease (CVD) is a major cause of mortality and morbidity in the Western world. CVD is mainly caused by atherosclerosis, for which dyslipidemia, characterized by high a plasma level of (very) low density lipoprotein ((V)LDL) and a low plasma level of high density lipoprotein (HDL), is a major risk factor. To reduce the risk to develop CVD, drugs aimed at correcting dyslipidemia by lowering (V)LDL are currently the first choice of treatment. Albeit that these drugs lower (V)LDL-C very efficiently (up to ~40%), and generally result in a slight increase in HDL-C, they only prevent a fraction of all cardiovascular events (~30%). Therefore new therapeutic strategies to reduce cardiovascular events more efficiently are necessary. Since HDL is has been attributed multiple protective effects in atherosclerosis by its role in reverse cholesterol transport and its anti-inflammatory and anti-oxidative properties, HDL-raising therapy is currently considered as a promising strategy to further reduce CVD risk. In this thesis, the mechanisms underlying the HDL-raising effects of the classical lipid-lowering drugs fenofibrate, atorvastatin and niacin were elucidated. Furthermore, the effects of potential novel HDL-raising strategies, including torcetrapib, PXR agonism and apoCI, on HDL metabolism were addressed. For these studies, we used the APOE*3-Leiden.CETP (E3L.CETP) transgenic mouse, a valuable model for human-like lipoprotein metabolism Show less
