The role of ApoCI, LPL and CETP in plasma lipoprotein metabolism - studies in mice

This thesis contributes to a better understanding of the roles of apoCI, LPL, and CETP in lipoprotein metabolism. Our data illustrate that the activity of LPL, and thereby the level of plasma TG, is crucially determined by the relative abundance of apolipoproteins. In addition, we showed that LPL is an important determinant in remnant-particle clearance in the absence of the three main apoE-recognizing receptors. Finally, we demonstrated that CETP presents a pro-atherogenic factor in mice resembling a human lipid distribution over lipoproteins and that atorvastatin and fenofibrate treatment influence HDL-metabolism via inhibition of CETP, which may thus add to their therapeutic benefit. Since there were initial concerns that inhibition of CETP would reduce the flux of cholesteryl esters from the periphery back to the liver, thereby possibly increasing the risk for atherosclerosis, it is of interest that we found that fenofibrate-mediated inhibition of CETP did not hamper the total flux of HDL-cholesteryl esters. This holds promise for therapies based on CETP inhibition.LEI Universiteit LeidenThe studies described in this thesis were supported by a grant from the Netherlands Organization of Scientific Research (NWO/ZonMW 908-02-097). The studies were performed at the Gaubius Laboratories of TNO-Quality of Life and the Leiden University Medical Center, the NetherlandsDe pathogenese, kliniek en behandeling van arterieel en veneus vaatlijde