Vol. 2 No. 1 (2016)
Review Article

Low Doses of Innate Defence Regulator Peptide, IDR-1018, Enhances HDL-Mediated Cholesterol Efflux from Smooth Muscle Cells and Macrophages

Afacan NJ
Department of Microbiology and Immunology, University of British Columbia, Canada
Chan T
Department of Medicine, Centre for Heart Lung Innovation, University of British Columbia, Canada
Pistolic J
EMBL Heidelberg, Germany
Kong J
Department of Medicine, Centre for Heart Lung Innovation, University of British Columbia, Canada
Francis GA
Department of Medicine, Centre for Heart Lung Innovation, University of British Columbia, Canada
Hancock REW
Department of Microbiology and Immunology, University of British Columbia, Canada
Published December 31, 2016

Abstract

Cardiovascular diseases due to atherosclerosis are the leading cause of death worldwide. In recent years, novel therapeutics designed to enhance high-density lipoprotein (HDL) activity as a treatment for atherosclerosis have been explored. Of particular interest is the use of amphipathic α-helical peptides to mimic the action of the main HDL protein, apolipoprotein (Apo)AI. Immunomodulatory peptides share many physical and functional properties with ApoAI and its mimetics; we therefore hypothesized that they too might be capable of enhancing cholesterol efflux. The aim of this study was to determine whether a potent immunomodulatory peptide, innate defence regulator (IDR)-1018, could promote cholesterol efflux from cells. Here, we report that IDR-1018 induced a dose-dependent increase in ApoAI on the cell surface and ATP-binding cassette transporter A1 (ABCA1) protein levels. Functional assays revealed that low doses of IDR-1018 improved HDL-mediated suppression of intracellular cholesteryl ester accumulation in macrophages and enhanced HDL-mediated cellular cholesterol efflux from smooth muscle cells and macrophages. Based on these results we propose that natural and synthetic immunomodulatory peptides like IDR-1018 represent a large new group of peptides that could be developed for the treatment of atherosclerosis.