title: Cationic peptides neutralize Ox-LDL, prevent its uptake by macrophages, and attenuate inflammatory response.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
authors.forename: Chandrakala
authors.initials: C
authors.lastname: Aluganti Narasimhulu
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
authors.forename: Krithika
authors.initials: K
authors.lastname: Selvarajan
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brown
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA. Electronic address: spartha@ucf.edu.
authors.forename: Sampath
authors.initials: S
authors.lastname: Parthasarathy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D003300:Copper / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D036341:Intercellular Signaling Peptides and Proteins; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D010538:Peritonitis / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D009195:Peroxidase / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C000597851:Gdn peptide; D036341:Intercellular Signaling Peptides and Proteins; C000597850:LL27 peptide; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D010455:Peptides; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; C431648:peptide 5F; D003300:Copper; D009195:Peroxidase
keywords: Atherosclerosis; Lipid peroxides; Lysine; Modified lipoproteins; Oxidation