You are carrying out a clinical trial of a new investigational drug for the treatment of hypercholesterolemia. Results of your studies indicate that consumption of the drug results in clear elevation in the level of circulating HDL in most of the test subjects. Given these results, which of the following proteins is most likely the target of the investigational drug?

Question

Quizplus · Accepted Answer

Inhibition of cholesterol ester transfer protein (CETP) is known to increase HDL levels, as CETP facilitates the transfer of cholesterol esters from HDL to other lipoproteins.  Cholesterol ester transfer protein (CETP) is plasma glycoprotein secreted primarily from the liver and plays a critical role in HDL metabolism by facilitating the exchange of cholesteryl esters (CE) from HDL for triglycerides (TG) in apoB- containing lipoproteins, such as LDL and VLDL. The activity of CETP directly lowers the cholesterol levels of HDL and enhances HDL catabolism by providing HDL with the TG substrate of hepatic lipase. Thus, CETP plays a critical role in the regulation of circulating levels of HDL, LDL, and apoA-I. It has also been shown that most of the cholesterol in mice, who naturally lack CETP, is found in HDL and these mice are relatively resistant to atherosclerosis. The potential for the therapeutic use of CETP inhibitors in humans was first suggested when it was discovered that a small Japanese population had an inborn error in the CETP gene, leading to hyperalphalipoproteinemia and very high HDL levels.

You Are Carrying Out a Clinical Trial of a New