Inducing apolipoprotein A-I synthesis to reduce cardiovascular risk: from ASSERT to SUSTAIN and beyond

Arch Med Sci. 2016 Dec 1;12(6):1302-1307. doi: 10.5114/aoms.2016.62906. Epub 2016 Oct 24.

Abstract

Increasing attention has focused on efforts to promote the biological activities of high-density lipoproteins (HDL) in order to reduce cardiovascular risk. Targeting apolipoprotein A-I (apoA-I), the major protein carried on HDL particles, represents an attractive approach to promoting HDL by virtue of its ability to increase endogenous synthesis of functional HDL particles. A number of pharmacological strategies that target apoA-I, including upregulation of its production with the bromodomain and extraterminal (BET) protein inhibitor RVX-208, development of short peptide sequences that mimic its action, and administration as a component of reconstituted HDL particles, have undergone clinical development. The impact of these approaches on cardiovascular biomarkers will be reviewed.

Keywords: apolipoprotein A-I; atherosclerosis; clinical trials; lipids; risk factors.