The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
NADPH Oxidase 1 Plays a Key Role in Diabetes Mellitus–Accelerated Atherosclerosis
Open accessAbstract
Background—: In diabetes mellitus, vascular complications such as atherosclerosis are a major cause of death. The key underlying pathomechanisms are unclear. However, hyperglycemic oxidative stress derived from NADPH oxidase (Nox), the only known dedicated enzyme to generate reactive oxygen species appears to play a role. Here we identify the Nox1 isoform as playing a key and pharmacologically targetable role in the accelerated development of diabetic atherosclerosis. Methods and Results—: Human aortic endothelial cells exposed to hyperglycemic conditions showed increased expression of Nox1, oxidative stress, and proinflammatory markers in a Nox1-siRNA reversible manner. Similarly, the specific Nox inhibitor, GKT137831, prevented oxidative stress in response to hyperglycemia in human aortic endothelial cells. To examine these observations in vivo, we investigated the role of Nox1 on plaque development in apolipoprotein E–deficient mice 10 weeks after induction of diabetes mellitus. Deletion of Nox1, but not Nox4, had a profound antiatherosclerotic effect correlating with reduced reactive oxygen species formation, attenuation of chemokine expression, vascular adhesion of leukocytes, macrophage infiltration, and reduced expression of proinflammatory and profibrotic markers. Similarly, treatment of diabetic apolipoprotein E–deficient mice with GKT137831 attenuated atherosclerosis development. Conclusions—: These studies identify a major pathological role for Nox1 and suggest that Nox1-dependent oxidative stress is a promising target for diabetic vasculopathies, including atherosclerosis.
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“Increased NOX1 activity is associated with vascular disease, and studies have shown links between high NOX1 levels and hypertension (1015), diabetes (163, 380, 1003), ischemia/reperfusion injury (479), and coronary artery disease (393).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [380]
In the citing paper
“Altogether, the role of NOX1 in cardiovascular disease seems secondary to NOX2, but still significant, as shown in several models (345, 380, 630, 854).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [380]
In the citing paper
“However, NOX4 deletion in the ApoE−/− mouse does not ameliorate diabetes-associated vasculopathy (380).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [380]
In the citing paper
“The results of different studies are contradictory, with examples of improved outcomes for NOX1 deficient mice subjected to high fat diet (854) and diabetic mouse models (380), whereas in other cases, NOX1 deletion did not seem to have an effect (875).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [380]
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Citations
Cites
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Superoxide Production and Expression of Nox Family Proteins in Human Atherosclerosis
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Vascular Adhesion Molecules in Atherosclerosis
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Nox4 Is a Protective Reactive Oxygen Species Generating Vascular NADPH Oxidase
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Self-citationA Noninvasive Computerized Tail-Cuff System for Measuring Blood Pressure in Mice
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Nox4 NAD(P)H Oxidase Mediates Hypertrophy and Fibronectin Expression in the Diabetic Kidney
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Di Marco, E., Gray, S. P., Kennedy, K., Szyndralewiez, C., Lyle, A. N., Lassègue, B., Griendling, K. K., Cooper, M. E., Schmidt, H. H. H. W., & Jandeleit-Dahm, K. A. M. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.07.013 · Cited by 67
Self-citationShahzad, K., Gadi, I., Nazir, S., Al-Dabet, M. M., Kohli, S., Bock, F., Breitenstein, L., Ranjan, S., Fuchs, T., Halloul, Z., et al. (2018) · Communications Biology · doi:10.1038/s42003-018-0108-5 · Cited by 40
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McCarty, M. (2015) · Healthcare · doi:10.3390/healthcare3020233 · Cited by 23
Sugur, K., Kempegowda, S. N., Shambu, S. K., Mahadevappa, M., Kengegowda, V. K., Gowda, J., & Thimmulappa, R. K. (2024) · Diabetes & Metabolic Syndrome: Clinical Research & Reviews · doi:10.1016/j.dsx.2024.103143 · Cited by 4
Metadata
- Authors
- Gray, S. P., Di Marco, E., Okabe, J., Szyndralewiez, C., Heitz, F., Montezano, A. C., de Haan, J. B., Koulis, C., El-Osta, A., Andrews, K. L., Chin-Dusting, J. P. F., Touyz, R. M., Wingler, K., Cooper, M. E., Schmidt, H. H. H. W., & Jandeleit-Dahm, K. A.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- From the Diabetic Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Australia (S.P.G., E.D.M., J.B.d.H., C.K., M.E.C., K.A.J.-D.); the Department of Medicine, Monash University, Monash, Australia (E.D.M., M.E.C., K.A.J.-D.); Epigenetics in Human Health and Disease, Baker IDI Heart & Diabetes Institute, Melbourne, Australia (J.O., A.E.-O.); GenKyoTex SA, Geneva, Switzerland (C.S., F.H.); Ottawa Hospital Research Institute, Ottawa, Canada (A.C.M., R.M.T.); Institute of...
- ORCID
- Venue
- Circulation
- Published
- 2013-05-07
- Volume
- 127
- Issue
- 18
- Pages
- 1888-1902
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2137012624
- Cited by
- 386
- References
- 56
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 24 · 2023: 17 · 2022: 20 · 2021: 29 · 2020: 41 · 2019: 28 · 2018: 24 · 2017: 33 · 2016: 37 · 2015: 43 · 2014: 39 · 2013: 16
- FWCI
- 31.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Diabetes Australia Research Trust
- Ottawa Hospital Research Institute
- Diabetes Australia
- National Heart Foundation of Australia
- Université de Genève
- Canadian Institutes of Health Research
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- NOX1, diabetic atherosclerosis, hyperglycemia, oxidative stress, reactive oxygen species, GKT137831, aortic endothelial cells, ApoE-deficient mice, atherosclerotic plaque, chemokine expression, leukocyte adhesion, macrophage infiltration, vascular inflammation
- MeSH terms
- NADPH Oxidase 1, Animals, Cells, Cultured, Diabetes Mellitus, Experimental, Humans, Male, Mice, Transgenic, NADH, NADPH Oxidoreductases, Organ Culture Techniques, Reactive Oxygen Species, Mice, Knockout, Inflammation Mediators, NADPH Oxidases, Protein Isoforms, Endothelial Cells, Atherosclerosis, Mice
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