Human carotid atherosclerotic plaque increases oxidative state of macrophages and low-density lipoproteins, whereas paraoxonase 1 (PON1) decreases such atherogenic effects
| Autor: | Hagai Tavori, Jacob Vaya, Soliman Khatib, Ramadan Musa, Michael Aviram, Aaron Hoffman, Samy Nitecki |
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| Rok vydání: | 2008 |
| Předmět: |
Carotid Artery Diseases
Cell Extracts medicine.medical_specialty Antioxidant medicine.medical_treatment Oxidative phosphorylation medicine.disease_cause Biochemistry Cell Line chemistry.chemical_compound Mice Physiology (medical) Internal medicine medicine Macrophage Animals Humans Carotid Stenosis biology Cholesterol Aryldialkylphosphatase Macrophages Paraoxonase PON1 Lipids Recombinant Proteins Lipoproteins LDL Oxidative Stress Endocrinology Carotid Arteries chemistry biology.protein Directed Molecular Evolution Oxidation-Reduction Oxidative stress Lipoprotein |
| Zdroj: | Free radical biologymedicine. 46(5) |
| ISSN: | 1873-4596 |
| Popis: | Human atherosclerotic plaque contains a variety of oxidized lipids, which can facilitate further oxidation. Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated esterase (lipolactonase), exhibiting antiatherogenic properties. The aims of the present study were to examine the oxidizing potency of the human carotid plaque lipid extract (LE), and the antiatherogenic role of PON1 on LE oxidation competence. Human carotid plaques were extracted by organic solvent, and the extract was incubated with lipoprotein particles, with macrophages, or with probes sensitive to oxidative stress, with or without preincubation with PON1, followed by oxidative-stress assessment. Our findings imply that the LE oxidized LDL, macrophages, and exogenous probes and decreases HDL-mediated cholesterol efflux from macrophages, in a dose-dependent manner. Incubation of PON1 with LE significantly affects LE composition, reduces LE atherogenic properties, and decreases the extract's total peroxide concentration by 44%, macrophage oxidation by 25%, and probe oxidation by up to 52%. We conclude that these results expand our understanding of how the plaque itself accelerates atherogenesis and provides an important mechanism for attenuation of atherosclerosis development by the antioxidant action of PON1 on the atherosclerotic plaque. |
| Databáze: | OpenAIRE |
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