Cited by 470Nitric Oxide and Endothelin EffectsAntioxidant Activity and Oxidative StressCardiovascular Health and Disease Prevention

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Is oxidative stress a therapeutic target in cardiovascular disease?

Münzel, Thomas, Gori, Tommaso, Bruno, Rosa Maria, Taddei, Stefano·2010·European Heart Journal

DOI 10.1093/eurheartj/ehq396

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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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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
ORCID: Münzel, Thomas
Gori, Tommaso
Taddei, Stefano
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
DOI: 10.1093/eurheartj/ehq396
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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