Chandrakala Aluganti Narasimhulu1, Krithika Selvarajan1, Matthew Brown1, Sampath Parthasarathy2. 1. Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA. 2. Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA. Electronic address: spartha@ucf.edu.
Abstract
OBJECTIVE: Apolipoprotein A1 (ApoA1) and apolipoprotein E (ApoE) mimetic peptides have attracted attention due to their ability to reduce atherosclerosis and exhibit antioxidant, anti-inflammatory, and hypolipidemic properties. In this study, we tested whether three distinct and unrelated cationic peptides would inhibit the oxidation of lipoproteins and whether they would counteract and neutralize the negatively charged modified lipoproteins, inhibit their uptake and inflammation by macrophages. METHODS AND RESULTS: 5F-mimetic peptide of ApoA1, LL27 derived from the anti-microbial peptide hCAP, and a human glycodelin derived peptide were commercially synthesized. We noted that these three distinct cationic lysine-rich peptides, two of which were unrelated to any known apolipoproteins, inhibited copper-mediated oxidation of lipoproteins and reduced lipid peroxides in a lysine dependent manner. The peptides also retarded the electrophoretic mobility of previously oxidized LDL and acetylated LDL by virtue of their net positive charge. Pre-incubation of peptides with modified lipoproteins reduced the uptake of the latter by macrophages, thus preventing the formation of foam cells. The cationic peptides inhibited oxidized LDL (Ox-LDL)-induced inflammatory response both in vitro and in vivo. CONCLUSION: Based on these results, we suggest that in addition to the well known mimetic peptides, other suitable cationic peptides may be of use for controlling Ox-LDL mediated inflammation and atherosclerotic progression.
OBJECTIVE:Apolipoprotein A1 (ApoA1) and apolipoprotein E (ApoE) mimetic peptides have attracted attention due to their ability to reduce atherosclerosis and exhibit antioxidant, anti-inflammatory, and hypolipidemic properties. In this study, we tested whether three distinct and unrelated cationic peptides would inhibit the oxidation of lipoproteins and whether they would counteract and neutralize the negatively charged modified lipoproteins, inhibit their uptake and inflammation by macrophages. METHODS AND RESULTS: 5F-mimetic peptide of ApoA1, LL27 derived from the anti-microbial peptide hCAP, and a humanglycodelin derived peptide were commercially synthesized. We noted that these three distinct cationic lysine-rich peptides, two of which were unrelated to any known apolipoproteins, inhibited copper-mediated oxidation of lipoproteins and reduced lipid peroxides in a lysine dependent manner. The peptides also retarded the electrophoretic mobility of previously oxidized LDL and acetylated LDL by virtue of their net positive charge. Pre-incubation of peptides with modified lipoproteins reduced the uptake of the latter by macrophages, thus preventing the formation of foam cells. The cationic peptides inhibited oxidized LDL (Ox-LDL)-induced inflammatory response both in vitro and in vivo. CONCLUSION: Based on these results, we suggest that in addition to the well known mimetic peptides, other suitable cationic peptides may be of use for controlling Ox-LDL mediated inflammation and atherosclerotic progression.
Authors: Diego Milani; Megan C Bakeberg; Jane L Cross; Vince W Clark; Ryan S Anderton; David J Blacker; Neville W Knuckey; Bruno P Meloni Journal: PLoS One Date: 2018-03-07 Impact factor: 3.240
Authors: Gabriella MacDougall; Ryan S Anderton; Amy Trimble; Frank L Mastaglia; Neville W Knuckey; Bruno P Meloni Journal: Molecules Date: 2020-06-29 Impact factor: 4.411