Cholesteryl ester transfer protein inhibitors

Whether CETP contributes to atherosclerosis or plays an antiatherogenic role is a controversial topic.16 In human plasma, CETP plays a potentially proatherogenic role by moving cholesteryl ester from HDL into VLDL and LDL particles, thereby lowering atheroprotective HDLc and raising proatherogenic VLDLc and LDLc. This equilibrium should be driven by the overall plasma concentration of CETP, and higher plasma CETP protein levels should therefore induce greater amounts of proatherogenic LDLc. On the other hand, CETP also plays a potentially key antiatherogenic role in the RCT process (Figure 4). By transferring cholesteryl ester from HDL to LDL and VLDL, CETP helps remove excess cholesterol from peripheral tissues (including atherosclerotic plaque) and increases the amount of cholesterol in these apoB lipoproteins that is taken up by the liver through the hepatic LDLr. Higher CETP plasma levels should therefore facilitate cholesterol removal by the RCT process.

A CETP inhibitor might be expected to raise plasma HDLc levels, lower LDLc, and provide a potential therapeutic benefit for the large number of patients at risk for CHD, because of low plasma HDLc levels. Recently, several new CETP inhibitors86,87 have entered clinical trials, and two have now independently demonstrated phase II proof of concept by dramatically increasing HDLc levels by 50% or more in healthy volunteers and patients with low HDLc.88,89 Thus, for the first time, pharmacological agents may be available that have the potential to elevate HDLc in patients with low HDLc to the same extent that the current standard-of-care drugs reduce LDLc in hyperlipidemic patients.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

Get My Free Ebook

Post a comment