The Role of Cholesteryl Ester Transfer Protein (CETP) in HDL Metabolism

Publisher Summary This chapter discusses the role of cholesteryl ester transfer protein (CETP) in high density lipoprotein (HDL) metabolism. CETP exchanges neutral lipids and phospholipids between lipoproteins. CETP-mediated exchange of neutral lipids results in the net mass transfer of triglycerides from triglyceride-rich very low density lipoproteins (VLDL) to HDL and the net transfer of cholesteryl esters from HDL to VLDL. This study reveals that CETP-mediated net mass transfers occur in the lipoprotein milieu in blood. The CETP-mediated exchange of neutral lipids changes the molecular structure of lipoproteins. Because HDL is smallest in size of the various lipoprotein classes, and therefore has fewer neutral lipids per particle, it is the movement of neutral lipids in and out of these particles that has particularly profound effects. These effects change HDL structure and consequently function and metabolism. The study also reveals that a combination of data obtained from transgenic research animals, different animal species, CETP-deficient humans, epidemiology, inhibitors of CETP, and in vitro studies provides ample evidence that CETP activity has fundamental effects on HDL metabolism. The most consistent effect is that CETP activity reduces plasma HDL cholesteryl ester concentration via neutral lipid exchange with other lipoproteins. This is primarily viewed as an atherosclerosis promoting effect due to the independent inverse association between HDL cholesterol and atherosclerosis risk. However, the link between CETP, HDL metabolism, and atherosclerosis is not independent of other modulators of lipid metabolism and atherogenesis.