Cited by 383Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressCardiovascular Health and Disease Prevention

Redox Control of Endothelial Function and Dysfunction: Molecular Mechanisms and Therapeutic Opportunities

Thomas, Shane R., Witting, Paul K., Drummond, Grant R.·2008·Antioxidants & Redox Signaling

Abstract

The endothelium is essential for the maintenance of vascular homeostasis. Central to this role is the production of endothelium-derived nitric oxide (EDNO), synthesized by the endothelial isoform of nitric oxide synthase (eNOS). Endothelial dysfunction, manifested as impaired EDNO bioactivity, is an important early event in the development of various vascular diseases, including hypertension, diabetes, and atherosclerosis. The degree of impairment of EDNO bioactivity is a determinant of future vascular complications. Accordingly, growing interest exists in defining the pathologic mechanisms involved. Considerable evidence supports a causal role for the enhanced production of reactive oxygen species (ROS) by vascular cells. ROS directly inactivate EDNO, act as cell-signaling molecules, and promote protein dysfunction, events that contribute to the initiation and progression of endothelial dysfunction. Increasing data indicate that strategies designed to limit vascular ROS production can restore endothelial function in humans with vascular complications. The purpose of this review is to outline the various ways in which ROS can influence endothelial function and dysfunction, describe the redox mechanisms involved, and discuss approaches for preventing endothelial dysfunction that may highlight future therapeutic opportunities in the treatment of cardiovascular disease.

Integrity signals

Registry

Crossref · 10.1089/ars.2008.2027

Cites

584 of 584 references verified0 citation errors · 0 not checkable

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  • Elevated reactive oxygen species lead to endothelial dysfunction, an early event in atherosclerosis pathogenesis that occurs mainly during atherosclerotic lesion formation.

    “Indeed, elevated ROS levels lead to endothelial dysfunction171, an early event in atherosclerosis pathogenesis that occurs mainly in atherosclerotic lesion formation172,173.”

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Authors
Thomas, S. R., Witting, P. K., & Drummond, G. R.
Affiliations
  • UNSW Sydney (AU)
  • Concord Repatriation General Hospital (AU)
  • Monash University (AU)
Venue
Antioxidants & Redox Signaling
Published
2008-10
Volume
10
Issue
10
Pages
1713-1766
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W2014374142
Cited by
383
References
577
Citations by year
2026: 7 · 2025: 7 · 2024: 9 · 2023: 7 · 2022: 18 · 2021: 12 · 2020: 20 · 2019: 13 · 2018: 13 · 2017: 24 · 2016: 23 · 2015: 17 · 2014: 38 · 2013: 22 · 2012: 42
FWCI
4.00
Type
journal article
Language
en
Open access
closed
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Keywords
endothelial dysfunction, endothelial function, reactive oxygen species, nitric oxide, endothelial nitric oxide synthase, redox signaling, vascular homeostasis, hypertension, diabetes mellitus, atherosclerosis, cardiovascular disease, antioxidant therapy
MeSH terms
Angiotensin-Converting Enzyme Inhibitors, Animals, Antioxidants, Endothelium, Vascular, Humans, Hydrogen Peroxide, Mitochondria, Nitric Oxide, Oxidation-Reduction, Oxidoreductases, Phosphoric Monoester Hydrolases, Protein Kinases, Superoxides, Thioredoxins, Transcription Factors, Vascular Diseases, Lipid Peroxidation, Oxidative Stress, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Endothelial Cells, Nitric Oxide Synthase Type III

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