The DOI matches its Crossref record; 155 of the 155 references it cites were found in a registry or an index.
eNOS Uncoupling in Cardiovascular Diseases - the Role of Oxidative Stress and Inflammation
Abstract
Many cardiovascular diseases and drug-induced complications are associated with - or even based on - an imbalance between the formation of reactive oxygen and nitrogen species (RONS) and antioxidant enzymes catalyzing the break-down of these harmful oxidants. According to the "kindling radical" hypothesis, the formation of RONS may trigger in certain conditions the activation of additional sources of RONS. According to recent reports, vascular dysfunction in general and cardiovascular complications such as hypertension, atherosclerosis and coronary artery diseases may be connected to inflammatory processes. The present review is focusing on the uncoupling of endothelial nitric oxide synthase (eNOS) by different mechanisms involving so-called "redox switches". The oxidative depletion of tetrahydrobiopterin (BH4), oxidative disruption of the dimeric eNOS complex, S-glutathionylation and adverse phosphorylation as well as RONS-triggered increases in levels of asymmetric dimethylarginine (ADMA) will be discussed. But also new concepts of eNOS uncoupling and state of the art detection of this process will be described. Another part of this review article will address pharmaceutical interventions preventing or reversing eNOS uncoupling and thereby normalize vascular function in a given disease setting. We finally turn our attention to the inflammatory mechanisms that are also involved in the development of endothelial dysfunction and cardiovascular disease. Inflammatory cell and cytokine profiles as well as their interactions, which are among the kindling mechanisms for the development of vascular dysfunction will be discussed on the basis of the current literature.
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In the citing paper
“According to the kindling hypothesis of endothelial dysfunction, the initial formation of ROS by other sources can promote uncoupling of NOS, amplifying the initial excess of ROS (488).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [488]
In the citing paper
“As such, the uncoupling of eNOS has been noted as a target for therapeutic potential (488, 569, 570, 600, 784).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [488]
In the citing paper
“As discussed in previous section, increased ROS eventually causes eNOS uncoupling via BH4 depletion, Zn/S cluster breakdown, and other routes, further perpetuating the generation of superoxide and other ROS (FIGURE 17) (488, 570).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [488]
Citations
Cites
1 retracted
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Cited by
Sorted by citations
Xu, S., Ilyas, I., Little, P. J., Li, H., Kamato, D., Zheng, X., Luo, S., Li, Z., Liu, P., Han, J., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000096 · Cited by 1,205
Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease
Steven, S., Frenis, K., Oelze, M. W., Kalinovic, S., Kuntić, M., Jiménez, M. T. B., Vujačić-Mirski, K., Helmstädter, J., Kröller‐Schön, S., Münzel, T. F., et al. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/7092151 · Cited by 756
Self-citationReactive oxygen species (ROS) in macrophage activation and function in diabetes
Rendra, E., Riabov, V., Mossel, D. M., Sevastyanova, T., Harmsen, M. C., & Kzhyshkowska, J. (2019) · Immunobiology · doi:10.1016/j.imbio.2018.11.010 · Cited by 636
Nitric Oxide and Endothelial Dysfunction
Cyr, A. R., Huckaby, L. V., Shiva, S. S., & Zuckerbraun, B. S. (2020) · Critical Care Clinics · doi:10.1016/j.ccc.2019.12.009 · Cited by 712
Oxidative Stress and Hypertension
Griendling, K. K., Camargo, L. L., Rios, F. J. O., Alves-Lopes, R., Montezano, A. C. I., & Touyz, R. M. (2021) · Circulation Research · doi:10.1161/circresaha.121.318063 · Cited by 618
Metadata
- Authors
- Karbach, S., Wenzel, P., Waisman, A., Munzel, T., & Daiber, A.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2014-06
- Volume
- 20
- Issue
- 22
- Pages
- 3579-3594
- ISSN
- 1381-6128 (ISSN-L)
- OpenAlex
- W2157350806
- Cited by
- 307
- References
- 155
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 21 · 2023: 20 · 2022: 34 · 2021: 40 · 2020: 26 · 2019: 23 · 2018: 23 · 2017: 29 · 2016: 19 · 2015: 24 · 2014: 7
- FWCI
- 17.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Pharmaceutical Design (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- endothelial nitric oxide synthase, eNOS uncoupling, oxidative stress, inflammation, tetrahydrobiopterin, S-glutathionylation, asymmetric dimethylarginine, reactive oxygen and nitrogen species, endothelial dysfunction, hypertension, atherosclerosis, coronary artery disease, vascular dysfunction, cytokines, redox switch
- MeSH terms
- Cardiovascular Diseases, Humans, Inflammation, Oxidative Stress, Nitric Oxide Synthase Type III
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