Cited by 1,618Nitric Oxide and Endothelin EffectsAntioxidant Activity and Oxidative StressRedox biology and oxidative stress

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Oxidative Stress and Vascular Disease

Madamanchi, Nageswara R., Vendrov, Aleksandr, Runge, Marschall S.·2005·Arteriosclerosis, Thrombosis, and Vascular Biology

DOI 10.1161/01.atv.0000150649.39934.13

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Abstract

Growing evidence indicates that chronic and acute overproduction of reactive oxygen species (ROS) under pathophysiologic conditions is integral in the development of cardiovascular diseases (CVD). These ROS can be released from nicotinamide adenine dinucleotide (phosphate) oxidase, xanthine oxidase, lipoxygenase, mitochondria, or the uncoupling of nitric oxide synthase in vascular cells. ROS mediate various signaling pathways that underlie vascular inflammation in atherogenesis: from the initiation of fatty streak development through lesion progress to ultimate plaque rupture. Various animal models of oxidative stress support the notion that ROS have a causal role in atherosclerosis and other cardiovascular diseases. Human investigations also support the oxidative stress hypothesis of atherosclerosis. Oxidative stress is the unifying mechanism for many CVD risk factors, which additionally supports its central role in CVD. Despite the demonstrated role of antioxidants in cellular and animal studies, the ineffectiveness of antioxidants in reducing cardiovascular death and morbidity in clinical trials has led many investigators to question the importance of oxidative stress in human atherosclerosis. Others have argued that the prime factor for the mixed outcomes from using antioxidants to prevent CVD may be the lack of specific and sensitive biomarkers by which to assess the oxidative stress phenotypes underlying CVD. A better understanding of the complexity of cellular redox reactions, development of a new class of antioxidants targeted to specific subcellular locales, and the phenotype-genotype linkage analysis for oxidative stress will likely be avenues for future research in this area as we move toward the broader use of pharmacological and regenerative therapies in the treatment and prevention of CVD.

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Background
A Co-Culture System for Studying Cellular Interactions in Vascular Disease
Padmanaban, A. M., Ganesan, K., & Ramkumar, K. M. (2024) · Bioengineering · doi:10.3390/bioengineering11111090 · Cited by 23
Three Musketeers for Lowering Cholesterol: Statins, Ezetimibe and Evolocumab
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Effect of periodontal disease on oxidative stress markers in patients with atherosclerosis
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Critical role of nitric oxide in impeding COVID-19 transmission and prevention: a promising possibility
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Retinal Vascular Study Using OCTA in Subjects at High Genetic Risk of Developing Alzheimer’s Disease and Cardiovascular Risk Factors
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“These cells promote atherosclerotic plaque, inducing local inflammatory responses; accelerating the migration of smooth muscle cells from the intima to the media [53]; and synthesizing extracellular matrix proteins such as collagen, elastin and proteoglycans that lead to vascular remodeling and decreased flow [54].”
Background
Inflammation and oxidative stress, rather than hypoxia, are predominant factors promoting angiogenesis in the initial phases of atherosclerosis
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“Atherosclerosis involves lipid deposition, inflammation (2), oxidative stress (3), angiogenesis (4) and other pathological processes and is associated with hypertension, hyperglycaemia, aging and various other risk factors (5).”
Background
Real-time assessment of flow reversal in an eccentric arterial stenotic model
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“Hemodynamics, specifically, fluid shear stress, is intimately involved in vascular oxidative stress (Madamanchi et al., 2005) and atherosclerotic lesions (Davies et al.”
Background
PEP-1-MsrA ameliorates inflammation and reduces atherosclerosis in apolipoprotein E deficient mice
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“ROS, including superoxide anion, hydroxyl radical and hydrogen peroxide (H2O2), are constantly generated by cells as byproducts of normal metabolism and highly localized within the cells [5, 6].”
Background
Lactobacillus acidophilus maintained oxidative stress from reproductive organs in collagen-induced arthritic rats
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“ROS and oxidative stress are now believed to be leading underlying pathology linking varicocele with male infertility.[33-35]”
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The Effect of Trandolapril and Its Fixed-Dose Combination with Verapamil on Circulating Adhesion Molecules Levels in Hypertensive Patients with Type 2 Diabetes
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“A reduction of all SAM tested in both groups in our work was expected because angiotensin II increases oxidative stress and is a main inductor of the activation of NFkB (13).”
Background
Vascular architecture-on-chip: engineering complex blood vessels for reproducing physiological and heterogeneous hemodynamics and endothelial function
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Effects of Tetrahydrobiopterin Oral Treatment in Hypoxia‐Induced Pulmonary Hypertension in Rat
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Increased oxidative stress in patients with essential thrombocythemia.
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Mitochondrial and Metabolic Adaptations to Exercise-Induced Fluid Shear Stress in Endothelial Cells
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Anthocyanins Found in Pinot Noir Waste Induce Target Genes Related to the Nrf2 Signalling in Endothelial Cells
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“Increased ROS and RNS concentrations have been linked to the development of various diseases, including cancer and cardiovascular diseases [44,45].”
Background
Pathophysiological and clinical aspects of the circadian rhythm of arterial stiffness in diabetes mellitus: A minireview
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Associations between the CYBA 242C/T and the MPO –463G/A Polymorphisms, Oxidative Stress and Cardiovascular Disease in Chronic Kidney Disease Patients
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“Oxidative stress (OS) is a reflection of the imbalance between the in vivo generation of free radicals and the anti-oxidative capacity of surrounding tissue and has emerged as a contributor to vascular disease [”
Background
Evaluation of clinical activity and safety of Daflon 500 mg in type 2 diabetic female patients
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“, myocardial infraction), when fibrous plaques rupture, the formation and release of thrombi may ultimately occlude vessels (Madamanchi et al., 2005).”
Background
Acute stress show great influences on liver function and the expression of hepatic genes associated with lipid metabolism in rats
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“cardiovascular disease [17-20], it has also been found to inhibit metabolic functions such as lipid elimination and glycometabolism [5,6].”
Background
Arresting progressive atherosclerosis by immunization with an anti-glycosaminoglycan monoclonal antibody in apolipoprotein E-deficient mice
Delgado-Roche, L., Brito, V., Acosta, E., Pérez, A., Fernández, J. R., Hernández-Matos, Y., Griñán, T., Soto, Y., León, O. S., Marleau, S., et al. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.08.027 · Cited by 21
“The crucial link between OS and the onset and progression of atherosclerosis has been established in animal models and human studies [42,43].”
Background
Protective Effect of Folic Acid on Oxidative DNA Damage
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Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease
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“CAD is a chronic progressive disease of narrowing of the arteries which supply oxygen and nutrients to cardiac muscle and is directly related to endothelial dysfunction caused by oxidative stress [2].”
Background
The Role of sGC Stimulators and Activators in Heart Failure With Reduced Ejection Fraction
Cordwin, D. J., Berei, T. J., & Pogue, K. T. (2021) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/10742484211042706 · Cited by 21
“Oxidative stress has been shown to induce cardiovascular disease pathology, including HF.(16) Increased oxidative stress can affect the NO-sGC-cGMP pathway in numerous ways (see Figure 1).”
BackgroundInfluential
The endothelium and the pathogenesis of atherosclerosis
Channon, K. M. (2006) · Medicine · doi:10.1383/medc.2006.34.5.173 · Cited by 21
A Natural Polyphenol, Chlorogenic Acid, Attenuates Obesity-Related Metabolic Disorders in Male Rats via miR-146a-IRAK1-TRAF6 and NRF2-Mediated Antioxidant Pathways
Alenezi, R. F., Abdelkhalek, A., El‐Sayed, G., Peț, I., Ahmadi, M., Sherbini, E. S. E., Puscasiu, D. A., & Arisha, A. H. (2025) · Biomolecules · doi:10.3390/biom15081086 · Cited by 23
“Oxidative stress is integral to the progression of obesity-related conditions [7,11].”
An Increase of Plasma Advanced Oxidation Protein Products Levels Is Associated with Cardiovascular Risk in Incident Peritoneal Dialysis Patients: A Pilot Study
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“The majority of CV disease results from complications of atherosclerosis [19–22].”
Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction
Buzinari, T. C., Oishi, J., de Moraes, T. F., Vatanabe, I. P., Selistre-de-Araújo, H. S., Pestana, C. R., & Rodrigues, G. J. (2017) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2017.04.022 · Cited by 20
“…cardiovascular diseases and contributes to the development and progression of arterial hypertension and atherosclerosis, which can lead to the development of cardiac and cerebral ischemic diseases, myocardial infarction and heart failure (Yetik-Anacak and Catravas, 2006; Madamanchi et al., 2005).”
Background
Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation
Lepedda, A. J., & Formato, M. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/6169825 · Cited by 21
“Furthermore, some lines of evidence suggest that unstable plaques are also characterized by pronounced oxidative environment [5].”
Background
Effect of 950 MHz UHF electromagnetic radiation on biomarkers of oxidative damage, metabolism of UFA and antioxidants in the livers of young rats of different ages
Furtado-Filho, O. V., Borba, J. B., Dallegrave, A., Pizzolato, T. M., Henriques, J. A. P., Moreira, J. C. F., & Saffi, J. (2013) · International Journal of Radiation Biology · doi:10.3109/09553002.2013.817697 · Cited by 20
“2009), cardiovascular (Madamanchi et al. 2005), damages resulting from the Abstract Purpose: To assess the effect of 950 MHz ultra-high-frequency electromagnetic radiation (UHF EMR) on biomarkers of oxidative damage, as well as to verify the concentration of unsaturated fatty acids (UFA) and the expression of the cata…”
Background
Acrolein increases 5-lipoxygenase expression in murine macrophages through activation of ERK pathway
Kim, C. E., Lee, S. J., Seo, K. W., Park, H. M., Yun, J. W., Bae, J. U., Bae, S. S., & Kim, C. D. (2010) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2010.02.003 · Cited by 20
Antihyperlipidemic and Antioxidant Potential of Paeonia emodi Royle against High-Fat Diet Induced Oxidative Stress
Zargar, B. A., Masoodi, M. H., Ahmed, B., & Ganie, S. A. (2014) · ISRN Pharmacology · doi:10.1155/2014/182362 · Cited by 20
“These processes lead to the tethering, activation, and attachment of monocytes and T lymphocytes to the endothelial cells [3].”
Background
Structural and biochemical characteristics of arterial stiffness in patients with atherosclerosis and in healthy subjects
Zagura, M., Kals, J., Serg, M., Kampus, P., Zilmer, M., Jakobson, M., Unt, E., Lieberg, J., & Eha, J. (2012) · Hypertension Research · doi:10.1038/hr.2012.88 · Cited by 20
Alteration of p66shc is associated with endothelial dysfunction in the abdominal aortic coarctation of rats
Lee, S. K., Kim, H. S., Song, Y. J., Joo, H. K., Lee, J. Y., Lee, K. H., Cho, E., Cho, C., Park, J. B., & Jeon, B. H. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.06.026 · Cited by 20
“crease the bioavailability of endothelial derived nitric oxide (NO), thereby contributing to the impairment of endothelium-dependent relaxation in the vascular system [1–3].”
Background
Antioxidant and lipid-regulating effects of probucol combined with atorvastatin in patients with acute coronary syndrome.
Guo, Y.-S., Wang, C., Cao, J. J., Gao, J.-L., Zou, X., Ren, Y.-H., & Li, F. (2015) · PubMed Central · doi:10.3978/j.issn.2072-1439.2014.12.29 · Cited by 20
“Moreover, oxidative stress plays an important role in the various stages of thrombosis development (4).”
Background
Superoxide anion generation and oxidative stress in methylmercury-induced endothelial toxicity in vitro
Ghizoni, H., de Souza, V., Straliotto, M. R., Bem, A. F. D., Farina, M., & Hort, M. A. (2016) · Toxicology in Vitro · doi:10.1016/j.tiv.2016.10.010 · Cited by 20
Soy milk versus simvastatin for preventing atherosclerosis and left ventricle remodeling in LDL receptor knockout mice
dos Santos, L., Davel, A. P., Almeida, T. I. R., Almeida, M. R., Soares, E. A., Fernandes, G. J. M., de Magalhães, S. F., Baraúna, V. G., & Garcia, J. A. D. (2017) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20165854 · Cited by 20
“Lastly, simvastatin also prevented lipid profile changes, hyperinsulinemia, LVH and atheroma plaque area in the HL group.”
BackgroundInfluential
Modulation of the biomarkers of inflammation and oxidative stress by ruminant trans fatty acids and dairy proteins in vascular endothelial cells (HUVEC)
Silva, M. S. D., Bilodeau, J., Larose, J., Greffard, K., Julien, P., Barbier, O., & Rudkowska, I. (2017) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2017.09.016 · Cited by 20
Oxidative Stress Parameters and Its Associations With Arterial Stiffness in Competitive Powerlifting Athletes After 12-Week Supervised Strength Training
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“However, long-lasting or acute overproduction of reactive species and high-grade OxS is relevant for the development of cardiovascular diseases (24).”
Background
Amlodipine ameliorates endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats
He, X., Zhang, H., Zhao, M., Yang, J., Cheng, G., Sun, L., Li, D., Jiang, H., Zhao, Q., Yu, X., et al. (2011) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2011.05495.x · Cited by 20
“Considerable evidence has shown exaggerated production of ROS by the vascular wall in SHR.(36,37) ROS excess is a major determinant of impaired vascular endothelium in SHR.”
BackgroundInfluential
Sanguis draconis , a Dragon’s Blood Resin, Attenuates High Glucose-Induced Oxidative Stress and Endothelial Dysfunction in Human Umbilical Vein Endothelial Cells
Chang, Y., Chang, T.-C., Lee, J.-J., Chang, N.-C., Huang, Y., Choy, C., & Jayakumar, T. (2014) · The Scientific World JOURNAL · doi:10.1155/2014/423259 · Cited by 20
“ROS can modify endothelial function by a variety ofmechanisms, such as peroxidation of membrane lipids, activation of NF-κB, and decreasing the availability of nitric oxide (NO) [5].”
Background
Effect of sodium selenite treatment on platelet aggregation of streptozotocin-induced diabetic rats
Ersöz, G., Yakaryılmaz, A., & Turan, B. (2003) · Thrombosis Research · doi:10.1016/s0049-3848(03)00338-4 · Cited by 20

Authors: Madamanchi, N. R., Vendrov, A., & Runge, M. S.
Affiliations: University of North Carolina at Chapel Hill (US)
ORCID: Madamanchi, Nageswara R.
Vendrov, Aleksandr
Runge, Marschall S.
Venue: Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2005-01
Volume: 25
Issue: 1
Pages: 29-38
ISSN: 1079-5642 (ISSN-L)
1524-4636
DOI: 10.1161/01.atv.0000150649.39934.13
OpenAlex: W2109698138
Cited by: 1,618
References: 135
Citations by year: 2026: 47 · 2025: 46 · 2024: 42 · 2023: 53 · 2022: 61 · 2021: 62 · 2020: 73 · 2019: 73 · 2018: 57 · 2017: 75 · 2016: 78 · 2015: 105 · 2014: 111 · 2013: 104 · 2012: 95
FWCI: 7.02
Type: journal article
Language: en
Open access: closed
Locations: Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: oxidative stress, reactive oxygen species, atherosclerosis, vascular disease, cardiovascular disease, NADPH oxidase, xanthine oxidase, lipoxygenase, nitric oxide synthase uncoupling, vascular inflammation, atherogenesis, antioxidants, redox signaling, biomarkers, cardiovascular risk factors
MeSH terms: Animals, Humans, Vascular Diseases, Oxidative Stress

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