Differential effects of NOX4 and NOX1 on immune cell-mediated inflammation in the aortic sinus of diabetic ApoE−/− mice
Abstract
Oxidative stress and inflammation are central mediators of atherosclerosis particularly in the context of diabetes. The potential interactions between the major producers of vascular reactive oxygen species (ROS), NADPH oxidase (NOX) enzymes and immune-inflammatory processes remain to be fully elucidated. In the present study we investigated the roles of the NADPH oxidase subunit isoforms, NOX4 and NOX1, in immune cell activation and recruitment to the aortic sinus atherosclerotic plaque in diabetic ApoE−/− mice. Plaque area analysis showed that NOX4- and NOX1-derived ROS contribute to atherosclerosis in the aortic sinus following 10 weeks of diabetes. Immunohistochemical staining of the plaques revealed that NOX4-derived ROS regulate T-cell recruitment. In addition, NOX4-deficient mice showed a reduction in activated CD4+ T-cells in the draining lymph nodes of the aortic sinus coupled with reduced pro-inflammatory gene expression in the aortic sinus. Conversely, NOX1-derived ROS appeared to play a more important role in macrophage accumulation. These findings demonstrate distinct roles for NOX4 and NOX1 in immune-inflammatory responses that drive atherosclerosis in the aortic sinus of diabetic mice.
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In general, NOX4 shows protective effects in ApoE−/− mice.
“In general, NOX4 shows protective effects in ApoE−/− mice (194, 229, 230, 379, 552, 838).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [229]
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Jandeleit-Dahm, K. A. M. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab018 · Cited by 4 · see citing works
Self-citationNox4: From Discovery to Pathophysiology
Hecker, L., Kato, K., & Griendling, K. K. (2023) · Springer eBooks · doi:10.1007/978-3-031-23752-2_12 · Cited by 1 · see citing works
Pathogenesis of Macrovascular Complications in Diabetes
Østergaard, J. A., Block, T. J., Dahm, S. I., Khan, W., & Jandeleit-Dahm, K. A. M. (2024) · Wiley eBooks · doi:10.1002/9781119697473.ch46 · Cited by 1 · see citing works
Self-citationOxidative stress–call for papers
Ryan, M. J. (2016) · Clinical Science · doi:10.1042/cs20160619
FOXO1-Mediated NOX4 Expression is Required for Host to Defense in the Model of Ocular ToxoplasmosisPreprint
Zhou, W., Gao, F., Lee, J. H., Lee, I., Yuk, J., Cho, K. S., Lee, Y., & Cha, G. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3912952
- Authors
- Di Marco, E., Gray, S. P., Chew, P., Kennedy, K., Cooper, M. E., Schmidt, H. H. H. W., & Jandeleit-Dahm, K. A. M.
- Affiliations
- Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia
- Baker Heart and Diabetes Institute (AU)
- Maastricht University (NL)
- Corresponding author
- Chew, Phyllis
- Kennedy, Kit
- Venue
- Clinical Science
- Publisher
- Portland Press Ltd.
- Published
- 2016-06-29
- Volume
- 130
- Issue
- 15
- Pages
- 1363-1374
- ISSN
- 0143-5221 (ISSN-L)
- 1470-8736
- OpenAlex
- W2461909749
- Cited by
- 37
- References
- 55
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 1 · 2016: 1
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Science (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- NOX4, NOX1, NADPH oxidase, reactive oxygen species, atherosclerosis, diabetes mellitus, ApoE-deficient mice, immune cell recruitment, T cell activation, CD4+ T cells, macrophage accumulation, inflammation, oxidative stress
- MeSH terms
- NADPH Oxidase 1, NADPH Oxidase 4, Animals, Aortitis, Apolipoproteins E, Chemotaxis, Leukocyte, Diabetes Mellitus, Experimental, Immunity, Cellular, Macrophages, NADH, NADPH Oxidoreductases, Phenotype, Sinus of Valsalva, Signal Transduction, CD4-Positive T-Lymphocytes, Cytokines, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, Inflammation Mediators, NADPH Oxidases, Genetic Predisposition to Disease, Atherosclerosis, Plaque, Atherosclerotic
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