Immunohistochemical evidence for the myeloperoxidase/H2O2/halide system in human atherosclerotic lesions: Colocalization of myeloperoxidase and hypochlorite‐modified proteins
Abstract
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, Cu 2+‐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/H 2 O 2/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/H 2 O 2/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.
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Allopurinol and oxypurinol have limited capacity to inhibit XO bound to glycosaminoglycans.
“It has also been pointed out that allopurinol and oxypurinol have limited capacity to inhibit XO bound to glycosaminoglycans (620).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [620]
The activity of febuxostat is not impaired by XO immobilization on the surface of ECs.
“Notably, the activity of febuxostat is not impaired by XO immobilization on the surface of ECs (620).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [620]
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Self-citation
- Authors
- Malle, E., Waeg, G., Schreiber, R., Gröne, E. F., Sattler, W., & Gröne, H.
- Affiliations
- University of Graz (AT)
- German Cancer Research Center (DE)
- Corresponding author
- Malle, Ernst
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 2000-07
- Volume
- 267
- Issue
- 14
- Pages
- 4495-4503
- ISSN
- 0014-2956 (ISSN-L)
- 1432-1033
- OpenAlex
- W1515001810
- Cited by
- 245
- References
- 60
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 10 · 2023: 4 · 2022: 8 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 9 · 2016: 10 · 2015: 9 · 2014: 7 · 2013: 9 · 2012: 8
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- myeloperoxidase, hypochlorous acid, atherosclerosis, LDL oxidation, modified lipoproteins, fibroatheroma, macrophages, foam cells, monoclonal antibodies, immunohistochemistry, oxidative stress, chronic inflammation, extracellular matrix
- MeSH terms
- Aged, Antibodies, Monoclonal, Epitopes, Aorta, Arteriosclerosis, Dose-Response Relationship, Immunologic, Electrophoresis, Polyacrylamide Gel, Endothelium, Vascular, Enzyme-Linked Immunosorbent Assay, Female, Femoral Artery, Humans, Hydrogen Peroxide, Hypochlorous Acid, Immunohistochemistry, Lipoproteins, LDL, Male, Middle Aged, Peroxidase, Oxygen, Ultracentrifugation, Blotting, Western, Tibial Arteries
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