Cholesteryl ester transfer protein inhibition as a strategy to reduce cardiovascular risk

作者: Philip J. Barter , Kerry-Anne Rye

DOI: 10.1194/JLR.R024075

关键词: EvacetrapibCholesterylester transfer proteinCholesterolLipoproteinTorcetrapibCETP inhibitorDalcetrapibAnacetrapibBiochemistryPharmacologyChemistry

摘要: Human and rabbit plasma contain a cholesteryl ester transfer protein (CETP) that promotes net mass transfers of esters from high density lipoproteins (HDL) to other lipoprotein fractions. As predicted, inhibition CETP in both humans rabbits increases the concentration cholesterol potentially protective HDL fraction, while decreasing it proatherogenic non-HDL Inhibition also inhibits development diet-induced atherosclerosis. However, use inhibitor torcetrapib did not reduce atheroma three imaging trials caused an excess deaths cardiovascular events large clinical outcome trial. The precise explanation for harm by is unknown but may relate documented, harmful effects unrelated CETP. More recently, trial using weak dalcetrapib, which raises levels less effectively than does lower levels, was terminated early reasons futility. There no evidence dalcetrapib Despite these setbacks, hypothesis inhibitors will be antiatherogenic still being tested studies with anacetrapib evacetrapib, two are much more potent do share off-target adverse torcetrapib.

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