Calcium-Dependent NOX5 Nicotinamide Adenine Dinucleotide Phosphate Oxidase Contributes to Vascular Oxidative Stress in Human Coronary Artery Disease
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Objectives This study sought to examine the expression and activity of the calcium-dependent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in human atherosclerotic coronary arteries.Background The NOX-based NADPH oxidases are major sources of reactive oxygen species (ROS) in human vessels. Several NOX homologues have been identified, but their relative contribution to vascular ROS production in coronary artery disease (CAD) is unclear; NOX5 is a unique homolog in that it is calcium dependent and thus could be activated by vasoconstrictor hormones. Its presence has not yet been studied in human vessels.Methods Coronary arteries from patients undergoing cardiac transplantation with CAD or without CAD were studied; NOX5 was quantified and visualized using Western blotting, immunofluorescence, and quantitative real-time polymerase chain reaction. Calcium-dependent NADPH oxidase activity, corresponding greatly to NOX5 activity, was measured by electron paramagnetic resonance.Results Both Western blotting and quantitative real-time polymerase chain reaction indicated a marked increase in NOX5 protein and messenger ribonucleic acid (mRNA) in CAD versus non-CAD vessels. Calcium-dependent NADPH-driven production of ROS in vascular membranes, reflecting NOX5 activity, was increased 7-fold in CAD and correlated significantly with NOX5 mRNA levels among subjects. Immunofluorescence showed that NOX5 was expressed in the endothelium in the early lesions and in vascular smooth muscle cells in the advanced coronary lesions.Conclusions These studies identify NOX5 as a novel, calcium-dependent source of ROS in atherosclerosis.
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Higher NOX5 expression levels have been observed in patients with coronary artery disease, but causation has not been proven.
“Higher NOX5 expression levels have been observed in patients with coronary artery disease (391), but causation has not been proven.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [391]
NOX-5-derived superoxide radical formation is associated with cardiovascular diseases in humans.
“For example, NOX-5-derived superoxide radical formation is associated with cardiovascular diseases in humans (Guzik et al. 2008).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Guzik et al. 2008
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- Authors
- Guzik, T. J., Chen, W., Gongora, M. C., Guzik, B., Lob, H. E., Mangalat, D., Hoch, N., Dikalov, S., Rudzinski, P., Kapelak, B., Sadowski, J., & Harrison, D. G.
- Affiliations
- Jagiellonian University (PL)
- Emory University (US)
- Corresponding author
- Harrison, David G.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 52
- Issue
- 22
- Pages
- 1803-1809
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC2593790
- OpenAlex
- W2138423356
- Cited by
- 281
- References
- 22
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 15 · 2023: 12 · 2022: 13 · 2021: 11 · 2020: 28 · 2019: 15 · 2018: 14 · 2017: 20 · 2016: 13 · 2015: 14 · 2014: 20 · 2013: 23 · 2012: 24
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL039006, HL 39000 6, T32HL007745, P01HL058000)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- NADPH oxidase 5, NADPH oxidase, reactive oxygen species, oxidative stress, coronary artery disease, atherosclerosis, endothelium, vascular smooth muscle cells, heart transplantation, human coronary arteries
- MeSH terms
- NADPH Oxidase 5, Calcium, Coronary Artery Disease, Coronary Vessels, Endothelium, Female, Humans, Male, Membrane Proteins, Middle Aged, Pilot Projects, Risk Factors, RNA, Messenger, Calcium Channels, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Myocytes, Smooth Muscle
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