Cited by 37Nitric Oxide and Endothelin EffectsAtherosclerosis and Cardiovascular DiseasesNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Differential effects of NOX4 and NOX1 on immune cell-mediated inflammation in the aortic sinus of diabetic ApoE−/− mice

Di Marco, Elyse, Gray, Stephen P., Chew, Phyllis, Kennedy, Kit, Cooper, Mark E., Schmidt, Harald H.H.W., Jandeleit-Dahm, Karin A.M.·2016·Clinical Science

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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Crossref · 10.1042/cs20160249

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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
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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