Evaluation of HDL modulating interventions for cardiovascular risk reduction using a systems pharmacology approach (original) (raw)

Journal of lipid research, 2015

Abstract

The recent failures of CETP inhibitor drugs to decrease cardiovascular disease (CVD) risk despite raising HDL cholesterol (HDL-C) levels suggest that pharmacologic increases in HDL-C may not always reflect elevations in reverse cholesterol transport (RCT), the process by which HDL is believed to exert its beneficial effects. HDL-modulating therapies can affect HDL properties beyond total HDL-C, including particle numbers, size and composition, and may contribute differently to RCT and CVD risk. The lack of validated, easily measurable pharmacodynamic markers to link drug effects to RCT and ultimately to CVD risk, complicates target and compound selection and evaluation. In this work, we use a systems pharmacology model to contextualize the roles of different HDL targets in cholesterol metabolism and provide quantitative links between HDL-related measurements and the associated changes in RCT rate, to support target and compound evaluation in drug development. By quantifying the amou...

Norman Mazer hasn't uploaded this paper.

Let Norman know you want this paper to be uploaded.

Ask for this paper to be uploaded.