The class
Review distinguishes humanized-mouse from rabbit models to find where CETP inhibition truly protects against atherosclerosis (Eur J Clin Invest 2016)
Original title: The controversy over the use of cholesteryl ester transfer protein inhibitors: is there some light at the end of the tunnel?
This review surveys 28 human population studies, 11 studies in mice expressing human CETP, and seven drug-inhibition studies in animals (six rabbits, one mouse) to resolve conflicting evidence on whether CETP inhibition prevents atherosclerosis. It finds that humanized-CETP mouse models are not illuminating, since they report both increases and decreases in atherosclerosis depending on the study. In contrast, investigations in rabbits and mice with severe hypercholesterolaemia consistently show that impairing CETP activity protects against atherosclerosis development, with substantial reductions in atherogenic apoB-containing lipoproteins across these experiments. The author concludes that the benefit of CETP inhibitors in preventing atherosclerosis is likely to be realised specifically in cases of hyperlipidaemia.
Original abstract
Background: According to epidemiological studies, there is no clear relationship between the plasma cholesteryl ester transfer protein (CETP) concentration and the development of atherosclerosis in human populations. Although some studies suggest that increased CETP activity relates to undesirable profiles of plasma lipoproteins, promoting an anti-atherogenic plasma lipoprotein profile by drugs that inhibit CETP has not succeeded in preventing atherosclerosis in humans.
Materials And Methods: This review describes 28 investigations in human populations dealing with plasma CETP, 11 in mice that express human CETP and seven in animals (six in rabbits and one in mice) in which plasma CETP activity was inhibited by drugs.
Results: Present review shows that models in mice expressing human CETP are not illuminating because they report increase as well reduction of atherosclerosis. However, investigations in rabbits and mice that develop severe hypercholesterolaemia clearly indicate that impairment of the plasma CETP activity elicits protection against the development of atherosclerosis; in all of these experiments are attained substantial reductions of the atherogenic lipoproteins, namely, plasma apoB containing lipoproteins.
Conclusion: These models are strong indicators that the benefit in preventing atherosclerosis should be earned in cases of hyperlipidemia by CETP inhibitors.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.