Linked Life Data

10880973

Source:http://linkedlifedata.com/resource/pubmed/id/10880973

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2000-9-7
pubmed:abstractText
The 'oxidation theory' of atherosclerosis proposes that oxidation of low density lipoprotein (LDL) contributes to atherogenesis. Although the precise mechanisms of in vivo oxidation are widely unknown, increasing evidence suggests that myeloperoxidase (MPO, EC 1.11.1.7), a protein secreted by activated phagocytes, generates modified/oxidized (lipo)proteins via intermediate formation of hypochlorous acid (HOCl). In vitro generation of HOCl transforms lipoproteins into high uptake forms for macrophages giving rise to cholesterol-engorged foam cells. To identify HOCl-modified-epitopes in human plaque tissues we have raised monoclonal antibodies (directed against human HOCl-modified LDL) that do not cross-react with other LDL modifications, i.e. peroxynitrite-LDL, hemin-LDL, Cu2+-oxidized LDL, 4-hydroxynonenal-LDL, malondialdehyde-LDL, glycated-LDL, and acetylated-LDL. The antibodies recognized a specific epitope present on various proteins after treatment with OCl- added as reagent or generated by the MPO/H2O2/halide system. Immunohistochemical studies revealed pronounced staining for HOCl-modified-epitopes in fibroatheroma (type V) and complicated (type VI) lesions, while no staining was observed in aortae of lesion-prone location (type I). HOCl-oxidation-specific epitopes are detected in cells in the majority of atherosclerotic plaques but not in control segments. Staining was shown to be inside and outside monocytes/macrophages, endothelial cells, as well as in the extracellular matrix. A similar staining pattern using immunohistochemistry could be obtained for MPO. The colocalization of immunoreactive MPO and HOCl-modified-epitopes in serial sections of human atheroma (type IV), fibroatheroma (type V) and complicated (type VI) lesions provides further convincing evidence for MPO/H2O2/halide system-mediated oxidation of (lipo)proteins under in vivo conditions. We propose that MPO could act as an important link between the development of atherosclerotic plaque in the artery wall and chronic inflammatory events.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4495-503
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed-meshheading:10880973-Aged, pubmed-meshheading:10880973-Antibodies, Monoclonal, pubmed-meshheading:10880973-Aorta, pubmed-meshheading:10880973-Arteriosclerosis, pubmed-meshheading:10880973-Blotting, Western, pubmed-meshheading:10880973-Dose-Response Relationship, Immunologic, pubmed-meshheading:10880973-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:10880973-Endothelium, Vascular, pubmed-meshheading:10880973-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:10880973-Epitopes, pubmed-meshheading:10880973-Female, pubmed-meshheading:10880973-Femoral Artery, pubmed-meshheading:10880973-Humans, pubmed-meshheading:10880973-Hydrogen Peroxide, pubmed-meshheading:10880973-Hypochlorous Acid, pubmed-meshheading:10880973-Immunohistochemistry, pubmed-meshheading:10880973-Lipoproteins, LDL, pubmed-meshheading:10880973-Male, pubmed-meshheading:10880973-Middle Aged, pubmed-meshheading:10880973-Oxygen, pubmed-meshheading:10880973-Peroxidase, pubmed-meshheading:10880973-Tibial Arteries, pubmed-meshheading:10880973-Ultracentrifugation
pubmed:year
2000
pubmed:articleTitle
Immunohistochemical evidence for the myeloperoxidase/H2O2/halide system in human atherosclerotic lesions: colocalization of myeloperoxidase and hypochlorite-modified proteins.
pubmed:affiliation
Institute of Medical Biochemistry and Biochemistry, Karl-Franzens University Graz, Austria. ernst.malle@kfunigraz.ac.at
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't