Human monocytes and macrophages express NADPH oxidase 5; a potential source of reactive oxygen species in atherosclerosis
Abstract
Monocytes (Mon) and Mon-derived macrophages (Mac) orchestrate important oxidative and inflammatory reactions in atherosclerosis by secreting reactive oxygen species (ROS) due, in large part, to the upregulated NADPH oxidases (Nox). The Nox enzymes have been extensively investigated in human Mon and Mac. However, the expression and functional significance of the Nox5 subtypes is not known. We aimed at elucidating whether Nox5 is expressed in human Mon and Mac, and examine its potential role in atherosclerosis. Human monocytic THP-1 cell line and CD14(+) Mon were employed to search for Nox5 expression. RT-PCR, Western blot, lucigenin-enhanced chemiluminescence and dihydroethidium assays were utilized to examine Nox5 in these cells. We found that Nox5 transcription variants and proteins are constitutively expressed in THP-1 cells and primary CD14(+) Mon. Silencing of Nox5 protein expression by siRNA reduced the Ca(2+)-dependent Nox activity and the formation of ROS in Mac induced by A23187, a selective Ca(2+) ionophore. Exposure of Mac to increasing concentrations of IFNγ (5-100 ng/ml) or oxidized LDL (5-100 μg/ml) resulted in a dose-dependent increase in Nox5 protein expression and elevation in intracellular Ca(2+) concentration. Immunohistochemical staining revealed that Nox5 is present in CD68(+) Mac-rich area within human carotid artery atherosclerotic plaques. To the best of our knowledge, this is the first evidence that Nox5 is constitutively expressed in human Mon. Induction of Nox5 expression in IFNγ- and oxidized LDL-exposed Mac and the presence of Nox5 in Mac-rich atheroma are indicative of the implication of Nox5 in atherogenesis.
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Expression of NOX5 in VSMCs and in macrophages and monocytes can contribute to the development of atherosclerotic lesions.
“Expression of NOX5 in VSMCs and in macrophages and monocytes can contribute to the development of atherosclerotic lesions (622, 623).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [622]
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- Authors
- Manea, A., Manea, S.-A., Gan, A. M., Constantin, A., Fenyo, I. M., Raicu, M., Muresian, H., & Simionescu, M.
- Affiliations
- Romanian Academy (RO)
- Corresponding author
- Manea, Adrian
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 461
- Issue
- 1
- Pages
- 172-179
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1991804264
- Cited by
- 69
- References
- 30
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 10 · 2020: 6 · 2019: 14 · 2018: 8 · 2017: 7 · 2016: 5 · 2015: 3
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- UEFISCDI (PN-II-ID-PCE-2011-3-0548, PN-II-RU-TE-2011-3-0142)
- European Social Found (POSDRU/159/1.5/S/133391)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- NADPH oxidase 5, monocytes, macrophages, reactive oxygen species, atherosclerosis, atherogenesis, oxidized LDL, interferon-gamma, intracellular calcium, atherosclerotic plaque, CD14+ monocytes, THP-1 cells, CD68+ macrophages
- MeSH terms
- NADPH Oxidase 5, Cell Line, Humans, Macrophages, Membrane Proteins, Monocytes, Reactive Oxygen Species, NADPH Oxidases, Atherosclerosis
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