The DOI matches its Crossref record; 53 of the 54 references it cites were found in a registry or an index.
Is oxidative stress a therapeutic target in cardiovascular disease?
Abstract
An abnormal production of reactive oxygen species (ROS) and the subsequent decrease in vascular bioavailability of nitric oxide (NO) have long been proposed to be the common pathogenetic mechanism of the endothelial dysfunction, resulting from diverse cardiovascular risk factors such as hypercholesterolaemia, diabetes mellitus, chronic smoking, metabolic syndrome, and hypertension. Superoxide produced by the nicotinamide dinucleotide phosphate (NADPH) oxidase, mitochondrial sources, or the xanthine oxidase may react with NO, thereby resulting in excessive formation of peroxynitrite, a reactive nitrogen species that has been demonstrated to accelerate the atherosclerotic process by causing direct structural damage and by causing further ROS production. Despite this sound biological rationale and a number of pre-clinical and clinical lines of evidence, studies testing the effects of classical antioxidants such as vitamin C, vitamin E, or folic acid in combination with vitamin E have been disappointing. Rather, substances such as statins, angiotensin-converting enzyme inhibitors, or AT1-receptor blockers, which possess indirect antioxidant properties mediated by the stimulation of NO production and simultaneous inhibition of superoxide production (e.g. from the NADPH oxidase), have been shown to improve vascular function in pre-clinical and clinical studies and to reduce the incidence of cardiovascular events in patients with cardiovascular disease. Today, oxidative stress remains an attractive target for cardiovascular prevention and therapy. However, a deeper understanding of its source, and of its role in vascular pathology, is necessary before new trials are attempted.
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“Cardiovascular risk factors (e.g., hypercholesterolemia, diabetes mellitus) impair the synthesis and bioactivity of endothelium-derived NO (4, 5).”
From Dietary nitrate, nitric oxide, and restenosis (2011) · cites this paper as [5]
In the citing paper
“Their adverse effect on the NOS pathway is mediated by asymmetric dimethylarginine (ADMA; the endogenous antagonist of NO synthesis) and by the vascular generation of superoxide anion (O 2 -), which degrades NO to peroxynitrite anion (ONOO -) (4, 5).”
From Dietary nitrate, nitric oxide, and restenosis (2011) · cites this paper as [5]
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Cites
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly
Beckman, J. S., & Koppenol, W. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.5.c1424 · Cited by 5,513
Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study
Hertog, M. G. L., Feskens, E. J. M., Kromhout, D., Hertog, M. G. L., Hollman, P. C. H., Hertog, M. G. L., & Katan, M. (1993) · The Lancet · doi:10.1016/0140-6736(93)92876-u · Cited by 4,336
Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G., & Gluud, C. (2007) · JAMA · doi:10.1001/jama.297.8.842 · Cited by 2,275
Garg, U. C., & Hassid, A. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114081 · Cited by 2,154
Stephens, N. G., Parsons, A., Brown, M. J., Schofield, P. M., Kelly, F., Cheeseman, K., & Mitchinson, M. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90866-1 · Cited by 2,148
Heitzer, T., Schlinzig, T., Krohn, K., Meinertz, T., & Münzel, T. (2001) · Circulation · doi:10.1161/hc4601.099485 · Cited by 1,961
Self-citationHypercholesterolemia increases endothelial superoxide anion production.
Ohara, Y., Peterson, T. E., & Harrison, D. G. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116491 · Cited by 1,765
Pacher, P., Nivorozhkin, A., & Szabó, C. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.1.6 · Cited by 1,218
Mechanisms Underlying Endothelial Dysfunction in Diabetes Mellitus
Hink, U., Li, H., Mollnau, H., Oelze, M., Matheis, E., Hartmann, M., Skatchkov, M. P., Thaiss, F., Stahl, R. A. K., Warnholtz, A., et al. (2001) · Circulation Research · doi:10.1161/01.res.88.2.e14 · Cited by 1,191
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Metadata
- Authors
- Münzel, T., Gori, T., Bruno, R. M., & Taddei, S.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- University of Pisa (IT)
- Corresponding author
- Münzel, Thomas
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10-25
- Volume
- 31
- Issue
- 22
- Pages
- 2741-2748
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W1974850809
- Cited by
- 470
- References
- 54
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 21 · 2023: 25 · 2022: 21 · 2021: 33 · 2020: 42 · 2019: 32 · 2018: 26 · 2017: 30 · 2016: 32 · 2015: 46 · 2014: 44 · 2013: 39 · 2012: 35
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- oxidative stress, reactive oxygen species, nitric oxide bioavailability, endothelial dysfunction, NADPH oxidase, superoxide, peroxynitrite, xanthine oxidase, mitochondrial superoxide, antioxidants, statins, ACE inhibitors, angiotensin receptor blockers, atherosclerosis, cardiovascular disease prevention, cardiovascular disease treatment
- MeSH terms
- Antioxidants, Arginine, Cardiovascular Diseases, Endothelium, Vascular, Humans, Mitochondria, Prognosis, Prospective Studies, Risk Factors, Vitamins, Xanthine Oxidase, Reactive Oxygen Species, Oxidative Stress, Nitric Oxide Synthase, NADPH Oxidases, Polyphenols
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