Cholesteryl ester transfer protein's role in high-density lipoprotein metabolism: Insights from studies with transgenic mice

Abstract A substantial percentage of people who develop coronary artery atherosclerosis have plasma cholesterol levels in the “desirable” range. The principal lipid abnormality in most of these individuals is a low plasma high-density lipoprotein (HDL) level (HDL cholesterol levels of 35 mg/dL or less). As a result, low HDL levels are not only recognized as a risk factor for the disease, but are considered the single best predictor of an individual's likelihood of developing coronary heart disease. Yet we are only now beginning to understand what regulates plasma HDL levels and why they are low in some individuals. Cholesteryl ester transfer protein (CETP), a plasma protein that shuttles neutral lipids (cholesteryl esters and triglycerides) back and forth between lipoproteins in the circulation, appears to play a key role in HDL metabolism, and recent studies using transgenic mice expressing that protein have broadened our understanding of the metabolic pathways that control plasma HDL levels. In this article, we review some of the key observations regarding CETP's role in HDL metabolism, with special emphasis on the discoveries made using transgenic mice, and we discuss these observations in the context of a model linking plasma triglyceride metabolism with low HDL levels.