title: High density lipoproteins (HDL) and the oxidative hypothesis of atherosclerosis.
abstract: The oxidative hypothesis of atherosclerosis classically implies a central role for low density lipoprotein (LDL) oxidation. However, new antiatherogenic properties have been recognized for high density lipoproteins (HDL), apart from their ability to reverse cholesterol transport. Indeed, native HDL could protect LDL from oxidation, thereby minimizing the deleterious consequences of this process. Several mechanisms have been suggested to explain this protective role. Two HDL-associated enzymes, paraoxonase and PAF-acetylhydrolase, detoxify oxidized phospholipids produced by lipid peroxidation. In addition, HDL could reduce hydroperoxides to their corresponding hydroxides. It has also been suggested that HDL could inhibit oxidized LDL-induced transduction signals. However, in vivo HDL oxidation in the subendothelial space would favor the atherosclerotic process. Indeed, atherogenic properties of these oxidized HDL partly result from some loss of their cholesterol effluxing capacity and from an inactivation of the lecithin-cholesterol acyltransferase, which is a HDL-associated enzyme involved in reverse cholesterol transport. Finally, oxidized HDL could induce cholesterol accumulation in macrophages. Further in-depth investigation is needed to assess these antagonistic effects and their consequences for the atherosclerotic process.
authors.affiliation: Laboratoire de Biochimie Métabolique et Clinique, Faculté de Pharmacie (Paris V), France.
authors.forename: D
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.forename: P
authors.initials: P
authors.lastname: Thérond
authors.forename: J L
authors.initials: JL
authors.lastname: Beaudeux
authors.forename: J
authors.initials: J
authors.lastname: Peynet
authors.forename: A
authors.initials: A
authors.lastname: Legrand
authors.forename: J
authors.initials: J
authors.lastname: Delattre
mesh_terms: D001161:Arteriosclerosis / Q000503:physiopathology; D006801:Humans; D008075:Lipoproteins, HDL / Q000502:physiology*; D010084:Oxidation-Reduction
chemical_list: D008075:Lipoproteins, HDL