Hyperlipidemia, inflammation and atherosclerosis : roles of apolipoprotein C1 and cholesteryl ester transfer protein

The main cause of cardiovascular disease (CVD) is atherosclerosis. Several genes that affect atherosclerosis development have been identified by the use of genetically modified mice (i.e. transgenic and knock-out mouse models). Many of these genes exert their role in atherosclerosis development as a result of effects on lipoprotein metabolism and inflammation. Transgenic mouse models have also been proven to be suitable for evaluating the mechanisms underlying the anti-atherosclerotic action of experimental drugs aimed to reduce atherogenic lipoprotein levels. However, thus far no suitable animal model was present to evaluate the mechanism of action of anti-atherosclerotic effect of HDL-raising therapeutic strategies. In this thesis, we further explored the role of apolipoprotein CI (apoCI) and cholesteryl ester transfer protein (CETP) in lipoprotein metabolism, inflammation, and atherosclerosis. Furthermore, we developed a mouse model that will be suitable for testing potential high-density-lipoprotein (HDL) raising therapies as a novel strategy to treat CVD.LEI Universiteit LeidenTNO-Quality of Life, F. Hoffmann-la Roche Ltd., Merck, Sharp &Dohme B.V., Boehringer-Ingelheim B.V., Pfizer B.V., Hope Farms Woerden, Astra Zeneca B.V.Vasculaire biologie en interventi