Coronary Artery Superoxide Production and Nox Isoform Expression in Human Coronary Artery Disease
Open accessAbstract
Background— Oxidative stress plays important role in the pathogenesis of atherosclerosis and coronary artery disease (CAD). We aimed to determine the sources and selected molecular mechanisms of oxidative stress in CAD. Methods and Results— We examined basal and NAD(P)H oxidase-mediated superoxide (O 2 · − ) production using lucigenin chemiluminescence, ferricytochrome c and dihydroethidium fluorescence in human coronary arteries from 19 CAD and 17 non-CAD patients undergoing heart transplantation. NAD(P)H oxidase subunits and xanthine oxidase expression were measured. Superoxide production was greater in coronary arteries from patients with CAD, even in vessels without overt atherosclerotic plaques, and was doubled within branching points of coronary arteries. Studies using pharmacological inhibitors and specific substrates showed that NAD(P)H oxidases (60%) and xanthine oxidase (25%) are primary sources of O 2 · − in CAD. Losartan significantly inhibited superoxide production in coronary arteries. NAD(P)H oxidase activity and protein levels of the NADPH oxidase subunits p22phox, p67 phox , and p47 phox were significantly increased in CAD, as were mRNA levels for p22phox and nox2, and no NAD(P)H oxidase subunit mRNA levels correlated with NAD(P)H oxidase activity in vessels from individual patients. Activity and protein expression of xanthine oxidase were increased in CAD, whereas xanthine dehydrogenase levels were not changed. Conclusions— Increased expression and activity of NAD(P)H oxidase subunits and xanthine oxidase, in part mediated through angiotensin II and PKC-dependent pathways, are important mechanisms underlying increased oxidative stress in human coronary artery disease.
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XO is expressed in ECs.
“XO is expressed in ECs (393), and its activity is increased by angiotensin II (551), TNF-α, LPS (117, 311), IL-6, and hypoxia (410, 748).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [393]
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- Authors
- Guzik, T. J., Sadowski, J., Guzik, B., Jopek, A., Kapelak, B., Przybyłowski, P., Wierzbicki, K., Korbut, R., Harrison, D. G., & Channon, K. M.
- Affiliations
- Jagiellonian University (PL)
- From the Department of Cardiovascular Medicine (T.J.G., K.M.C.), University of Oxford, John Radcliffe Hospital, United Kingdom; Departments of Medicine, Cardiovascular Surgery, and Transplantology and Pharmacology (T.J.G., J.S., B.G., A.J., B.K., P.P., K.W., R.K.), Jagiellonian University School of Medicine, Krakow, Poland; and the Division of Cardiology (D.G.H., T.J.G.), Emory University, Atlanta, Ga.
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2006-02
- Volume
- 26
- Issue
- 2
- Pages
- 333-339
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2130904954
- Cited by
- 278
- References
- 22
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 9 · 2022: 8 · 2021: 12 · 2020: 10 · 2019: 9 · 2018: 6 · 2017: 23 · 2016: 15 · 2015: 14 · 2014: 20 · 2013: 21 · 2012: 18
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- green
- ruj.uj.edu.pl
- Licence
- cc-by-nc-nd
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
- Funders
- Wellcome Trust
- British Heart Foundation
- 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
- coronary artery disease, superoxide production, NADPH oxidase, xanthine oxidase, oxidative stress, NOX isoforms, p22phox, p67phox, p47phox, NOX2, angiotensin II, protein kinase C, losartan, human coronary arteries, atherosclerosis
- MeSH terms
- Adult, Angiotensin II, Coronary Artery Disease, Coronary Vessels, Female, Humans, Male, Middle Aged, Phosphoproteins, Protein Kinase C, Superoxides, Vasoconstrictor Agents, Xanthine Oxidase, Oxidative Stress, NADPH Oxidases, Membrane Transport Proteins
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