HDL biology
A review of PLTP and CETP in atherogenesis weighs the mixed record of CETP inhibitors against open questions about PLTP (Adv Clin Exp Med 2018)
Original title: Plasma lipid transfer proteins: The role of PLTP and CETP in atherogenesis
This review examines the roles of two plasma lipid transfer proteins, phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP), in the development of atherosclerosis. A lack of either protein raises HDL and lowers LDL levels, motivating the search for compounds that reduce CETP activity to cut cardiovascular risk. The review weighs the adverse effect seen with torcetrapib against the lack of therapeutic benefit reported for dalcetrapib, and asks whether CETP inhibitors still in clinical trials can meet the challenge. It also discusses PLTP's role in reverse cholesterol transport, noting ongoing contradictions in the literature about its net effect on HDL metabolism and atherogenesis.
Original abstract
Cardiovascular diseases are still the main cause of death in Poland and throughout the world. Independent risk factors of cardiovascular disease, in addition to elevated LDL cholesterol, are both low HDL levels and high levels of non-HDL cholesterol. Plasma phospholipid-transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) both play a major role in the metabolism of those lipoproteins. A lack of these proteins increases HDL and lowers LDL levels. In the light of current knowledge, it seems reasonable to search for compounds that may decrease the activity of CETP, and thus reduce the incidence of cardiovascular disease. Whereas on the one hand there are reports about the adverse effect of torcetrapib and the lack of therapeutic effects of dalcetrapib, on the other hand the question arises whether the CETP inhibitors that are currently in clinical trials will rise to the challenges before them. Currently, it is known that the activity of PLTP, while affecting the metabolism of lipoproteins, especially HDL, plays a major role in atherogenesis. Still, there are some contradictions and controversies about the effect of PLTP on reverse cholesterol transport (RCT). There are a number of studies about the role that PLTP plays in the pathogenesis of various diseases. Further studies are needed to clearly determine the impact of PLTP activity on the formation and development of pathological processes in the cardiovascular system.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.