Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). This paper describes a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) that binds to lipoproteins and stimulates cholesterol efflux, as well as a motif based on the last helix of apoC-II that activates lipolysis by LPL. The authors found that C-II-a peptide promoted cholesterol efflux from ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to activate lipolysis by LPL. Intravenous injection of C-II-a in apoE-knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides. When coinjected with an apoA-I mimetic peptide, the C-II-a peptide was found to completely block the hypertriglyceridemic effect.
See article at J Pharmacol Exp Ther 2015, 352:227–235.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics