Cholesteryl ester transfer protein and its inhibition

Abstract

Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that facilitates the transfer of cholesteryl esters from the atheroprotective high density lipoprotein (HDL) to the proatherogenic low density lipoprotein cholesterol (LDL) and very low density lipoprotein cholesterol (VLDL) leading to lower levels of HDL but raising the levels of proatherogenic LDL and VLDL. Inhibition of CETP is considered a potential approach to treat dyslipidemia. However, discussions regarding the role of CETP-mediated lipid transfer in the development of atherosclerosis and CETP inhibition as a potential strategy for prevention of atherosclerosis have been controversial. Although many animal studies support the hypothesis that inhibition of CETP activity may be beneficial, negative phase III studies on clinical endpoints with the CETP inhibitor torcetrapib challenged the future perspectives of CETP inhibitors as potential therapeutic agents. The review provides an update on current understanding of the molecular mechanisms involved in CETP activity and its inhibition.

Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity

“…On one hand, it increases LDL and very-lowdensity lipoproteins (VLDLs) levels by transferring cholesterol esters from high-density lipoproteins (HDLs) to LDLs/VLDLs. On the other hand, it increases removal of lipoproteins from the circulation as part of transferring triglycerides from VLDLs/LDLs to HDLs (reviewed in Weber et al 2010). Hence, one might expect the rare allele of rs9923854 (CETP) to contribute to decreased cholesterol ester transfer activity and/or increased triglyceride transfer activity, although the role could well be much more complex.…”

“…Hence, one might expect the rare allele of rs9923854 (CETP) to contribute to decreased cholesterol ester transfer activity and/or increased triglyceride transfer activity, although the role could well be much more complex. This is underlined by the difference in success observed in clinical studies of cetp inhibitors for prevention of atherosclerosis (Weber et al 2010).…”

Resveratrol in cardiovascular disease: what is known from current research?

“…Cholesteryl ester transfer protein (CETP) is a crucial enzyme of RCT. Raised CETP activity induces high LDL level, thus contributing to atherosclerosis [72,73]. Decreased CETP activity, elevated HDL level, and a promotion in the capacity of HDL to mediate cholesterol efflux have been observed with resveratrol treatment recently [29,71,73,74].…”

Association of the CETP TaqIB Polymorphism with Coronary Artery Disease in Type 2 Diabetic Patients

“…In general, the cardioprotective role of HDL-C is by its performance in the reverse cholesterol transport (CT), whereby the excessive cholesterol is transferred to liver for metabolism and secretion into the bile, and ultimately preventing atherosclerosis (5)(6)(7)(8). The cholesteryl ester transfer protein (CETP) is a glycoprotein with 476 amino acids and a molecular weight of 74 kDa facilitating the transfer of cholesteryl ester and TGs between anti-atherogenic HDL, pro-atherogenic LDL and VLDL particles (5,(9)(10)(11). CETP (Gene ID: 1071) is a 25 kb gene located on chromosome 16q12, adjacent to the lecithin cholesterol acyl transferase gene (16q12-16q21) (12,13).…”