title: The effect of HDL mimetic peptide 4F on PON1.
abstract: Several lines of evidence indicate that serum paraoxonase 1 (PON1) acts as an important guardian against cellular damage from oxidized lipids in plasma membrane, in low-density lipoprotein (LDL), against bacterial endotoxin and against toxic agents such as pesticide residues including organophosphates. In circulation, the high-density lipoprotein (HDL)-associated PON1 has the ability to prevent the formation of proinflammatory oxidized phospholipids. These oxidized phospholipids negatively regulate the activities of the HDL-associated PON1 and several other anti-inflammatory factors in HDL. During the acute phase response in rabbits, mice, and humans, there appears to be an increase in the formation of these oxidized lipids that results in the inhibition of the HDL-associated PON1 and an association of acute phase proteins with HDL that renders HDL proinflammatory. Low serum HDL is a risk factor for atherosclerosis and attempts are directed toward therapies to improve the quality and the relative concentrations of LDL and HDL. Apolipoprotein A-I (apoA-I) has been shown to reduce atherosclerotic lesions in laboratory animals. ApoA-I, however, is a large protein and needs to be administered parenterally, and it is costly. We have developed apoA-I mimetic peptides that are much smaller than apoA-I, and much more effective in removing the oxidized phospholipids and other oxidized lipids. These mimetic peptides improve LDL and HDL composition and function and reduce lesion formation in animal models of atherogenesis. Following is a brief description of some of the HDL mimetic peptides that can improve HDL and the effect of the peptide on PON1 activity.
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, CA, USA. lvakili@mednet.ucla.edu
authors.forename: Ladan
authors.initials: L
authors.lastname: Vakili
authors.forename: Susan
authors.initials: S
authors.lastname: Hama
authors.forename: J Brian
authors.initials: JB
authors.lastname: Kim
authors.forename: Duc
authors.initials: D
authors.lastname: Tien
authors.forename: Shila
authors.initials: S
authors.lastname: Safarpoor
authors.forename: Nancy
authors.initials: N
authors.lastname: Ly
authors.forename: Ghazal
authors.initials: G
authors.lastname: Vakili
authors.forename: Greg
authors.initials: G
authors.lastname: Hough
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000737:chemistry*; D050197:Atherosclerosis / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008055:Lipids / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000737:chemistry*; D051379:Mice; D010100:Oxygen / Q000737:chemistry; D010455:Peptides / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; C465468:D-4F peptide; D008055:Lipids; D008075:Lipoproteins, HDL; D010455:Peptides; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D010100:Oxygen