CETP Activity: A Link between Lipid Metabolism and Coagulation System

CETP is a hydrophobic glycoprotein secreted by the liver and is predominantly associated with apo A-I containing lipoproteins in the plasm. CETP plays important roles in modulating vascular lipoproteins. It facilitates the redistribution of cholesterol esters, phospholipids, and triglycerides between plasma lipoproteins. As a consequence of CETP-mediated transfer of cholesterol esters from HDL(high density lipoprotein) to LDL (low density lipoprotein) and VLDL(very low density lipoprotein), HDL is remodeled in its content and function. Because decreased level of HDL is the risk factor of coronary atherosclerotic disease, CETP inhibitors are developed and clinical trials were performed to prevent the progression of atherosclerotic lesion and cardiovascular events. However, all CETP inhibitors except anacetrapib failed to provide a positive effect and the development of these drugs was stopped. A possible reason of these results may be that CETP– HDL complex generated by CETP inhibitors could suppress the anti-atherogenic effects of HDL, such as anti-inflammatory, anti-thrombotic, or anti-oxidative functions.