The DOI matches its Crossref record; 84 of the 88 references it cites were found in a registry or an index.
Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions.
Open accessAbstract
Oxidatively modified lipoproteins have been implicated in atherogenesis, but the mechanisms that promote oxidation in vivo have not been identified. Myeloperoxidase, a heme protein secreted by activated macrophages, generates reactive intermediates that oxidize lipoproteins in vitro. To explore the potential role of myeloperoxidase in the development of atherosclerosis, we determined whether the enzyme was present in surgically excised human vascular tissue. In detergent extracts of atherosclerotic arteries subjected to Western blotting, a rabbit polyclonal antibody monospecific for myeloperoxidase detected a 56-kD protein, the predicted molecular mass of the heavy subunit. Both the immunoreactive protein and authentic myeloperoxidase bound to a lectin-affinity column; after elution with methyl mannoside their apparent molecular masses were indistinguishable by nondenaturing size-exclusion chromatography. Peroxidase activity in detergent extracts of atherosclerotic lesions likewise bound to a lectin column and eluted with methyl mannoside. Moreover, eluted peroxidase generated the cytotoxic oxidant hypochlorous acid (HOCl), indicating that enzymatically active myeloperoxidase was present in lesions. Patterns of immunostaining of arterial tissue with antihuman myeloperoxidase antibodies were similar to those produced by an antimacrophage antibody, and were especially prominent in the shoulder region of transitional lesions. Intense foci of myeloperoxidase immunostaining also appeared adjacent to cholesterol clefts in lipid-rich regions of advanced atherosclerotic lesions. These findings identify myeloperoxidase as a component of human vascular lesions. Because this heme protein can generate reactive species that damage lipids and proteins, myeloperoxidase may contribute to atherogenesis by catalyzing oxidative reactions in the vascular wall.
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“Macrophage localization in the atherosclerotic plaque leads to detectable MPO activity and products of HOCl oxidation (213, 414).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [213]
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Role of Oxidative Modifications in Atherosclerosis
Stocker, R., & Keaney, J. F. (2004) · Physiological Reviews · doi:10.1152/physrev.00047.2003 · Cited by 2,651
Myeloperoxidase: friend and foe
Klebanoff, S. J. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.1204697 · Cited by 2,282
Antimicrobial reactive oxygen and nitrogen species: concepts and controversies
Fang, F. C. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro1004 · Cited by 1,676
Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils
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Chronic Kidney Disease: Effects on the Cardiovascular System
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Metadata
- Authors
- Daugherty, A., Dunn, J. L., Rateri, D. L., & Heinecke, J. W.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1994-07-01
- Volume
- 94
- Issue
- 1
- Pages
- 437-444
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC296328
- OpenAlex
- W2028257547
- Cited by
- 1,269
- References
- 88
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 24 · 2023: 28 · 2022: 39 · 2021: 32 · 2020: 48 · 2019: 47 · 2018: 61 · 2017: 40 · 2016: 40 · 2015: 48 · 2014: 42 · 2013: 50 · 2012: 45
- FWCI
- 10.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (5r01hd029920-05)
- National Heart, Lung, and Blood Institute (HL-17646)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD-29920)
- 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 (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- myeloperoxidase, lipoprotein oxidation, atherosclerosis, atherosclerotic plaque, macrophages, hypochlorous acid, oxidized lipoproteins, atherogenesis, heme enzymes, cholesterol clefts, vascular wall
- MeSH terms
- Arteriosclerosis, Free Radicals, Humans, Hypochlorous Acid, Immunohistochemistry, Lipoproteins, Macrophages, Peroxidase
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