Cited by 307Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionRedox biology and oxidative stress

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eNOS Uncoupling in Cardiovascular Diseases - the Role of Oxidative Stress and Inflammation

Karbach, Susanne, Wenzel, Philip, Waisman, Ari, Munzel, Thomas, Daiber, Andreas·2014·Current Pharmaceutical Design

DOI 10.2174/13816128113196660748

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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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Authors: Karbach, S., Wenzel, P., Waisman, A., Munzel, T., & Daiber, A.
Affiliations: University Medical Center of the Johannes Gutenberg University Mainz (DE)
ORCID: Karbach, Susanne
Wenzel, Philip
Waisman, Ari
Daiber, Andreas
Venue: Current Pharmaceutical Design
Publisher: Bentham Science Publishers Ltd.
Published: 2014-06
Volume: 20
Issue: 22
Pages: 3579-3594
ISSN: 1381-6128 (ISSN-L)
DOI: 10.2174/13816128113196660748
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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eNOS Uncoupling in Cardiovascular Diseases - the Role of Oxidative Stress and Inflammation

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