High density lipoprotein is targeted for oxidation by myeloperoxidase in rheumatoid arthritis
| Autor: | Brenda W. Gillespie, Subramaniam Pennathur, Rajiv Saran, Mariana J. Kaplan, Jay W. Heinecke, Jaeman Byun, Robin L. Sands, Anuradha Vivekanandan-Giri, Jessica L. Slocum, Chongren Tang |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty Halogenation Immunology Oxidative phosphorylation Peptide Mapping Article General Biochemistry Genetics and Molecular Biology Arthritis Rheumatoid chemistry.chemical_compound High-density lipoprotein Rheumatology Tandem Mass Spectrometry Internal medicine medicine Humans Immunology and Allergy Aged Peroxidase Apolipoprotein A-I biology Cholesterol business.industry Case-control study nutritional and metabolic diseases Middle Aged medicine.disease Connective tissue disease Endocrinology chemistry Cardiovascular Diseases Case-Control Studies Myeloperoxidase Rheumatoid arthritis biology.protein Tyrosine Female lipids (amino acids peptides and proteins) Efflux Lipoproteins HDL business Oxidation-Reduction |
| Zdroj: | Annals of the Rheumatic Diseases. 72:1725-1731 |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | Objective Phagocyte-derived myeloperoxidase (MPO) and pro-inflammatory high density lipoprotein (HDL) associate with rheumatoid arthritis (RA), but the link between MPO and HDL has not been systematically examined. In this study, we investigated whether MPO can oxidise HDL and determined MPO-specific oxidative signature by apoA-1 by peptide mapping in RA subjects with and without known cardiovascular disease (CVD). Methods Two MPO oxidation products, 3-chlorotyrosine and 3-nitrotyrosine, were quantified by tandem mass spectrometry (MS/MS) in in vitro model system studies and in plasma and HDL derived from healthy controls and RA subjects. MPO levels and cholesterol efflux were determined. Site-specific nitration and chlorination of apoA-1 peptides were quantified by MS/MS. Results RA subjects demonstrated higher levels of MPO, MPO-oxidised HDL and diminished cholesterol efflux. There was marked increase in MPO-specific 3-chlorotyrosine and 3-nitrotyrosine content in HDL in RA subjects consistent with specific targeting of HDL, with increased nitration in RA subjects with CVD. Cholesterol efflux capacity was diminished in RA subjects and correlated inversely with HDL 3-chlorotyrosine suggesting a mechanistic role for MPO. Nitrated HDL was elevated in RACVD subjects compared with RA subjects without CVD. Oxidative peptide mapping revealed site-specific unique oxidation signatures on apoA-1 for RA subjects with and without CVD. Conclusions We report an increase in MPO-mediated HDL oxidation that is regiospecific in RA and accentuated in those with CVD. Decreased cholesterol efflux capacity due to MPO-mediated chlorination is a potential mechanism for atherosclerosis in RA and raises the possibility that oxidant resistant forms of HDL may attenuate this increased risk. |
| Databáze: | OpenAIRE |
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