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Oxidative Stress and Vascular Disease
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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“Additionally, studies show peroxynitrite can traverse cell membranes by both diffusion and through ion channels, suggesting that peroxynitrite can mediate oxidation/nitration distant from its site of formation (221, 611).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [611]
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“Additionally, studies show peroxynitrite can traverse cell membranes by both diffusion and through ion channels, suggesting that peroxynitrite can mediate oxidation/nitration distant from its site of formation (221, 611).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [611]
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“Oxidative stress, which is associated with enhanced production of reactive oxygen species including superoxide radical, hydrogen peroxide, and hydroxyl radical, is a common feature in different vascular diseases.(10) Among those, superoxide is the primary and most abundant reactive oxygen species generated by a number…”
BackgroundLombardo, F. P., Sgrò, P., Gandini, L., Dondero, F., Jannini, E. A., & Lenzi, A. (2004) · Journal of Endocrinological Investigation · doi:10.1007/bf03346286 · Cited by 13
Toma, C., Ferdeghini, D., Pour, M. M. O., Venkatesan, S., Cillà, S. D., & Grossini, E. (2026) · Antioxidants · doi:10.3390/antiox15040425 · Cited by 13
Antioxidant enzymes and vascular diseases
Radovanović, J., Banjac, K., Obradovic, M. M., & Isenović, E. R. (2021) · Exploration of Medicine · doi:10.37349/emed.2021.00070 · Cited by 14
“All these processes lead to vascular system diseases such as atherosclerosis and arterial hypertension [1].”
BackgroundInfluentialUeda, H., Inoue, K., Seki, R., Nemoto, Y., & Terawaki, H. (2023) · Clinical and Experimental Nephrology · doi:10.1007/s10157-023-02318-0 · Cited by 12
Mechanisms of SIRT3 Regulation of Aging and Aging-Related Diseases and Advances in Drug Therapy
Yang, J., Lu, Y., Zhao, Y. C., & Wang, X. (2025) · Gerontology · doi:10.1159/000547549 · Cited by 13
“Cardiac aging manifests as hypertrophy, fibrosis, accumulation of misfolded proteins, and mitochondrial dysfunction [72].”
Lee, B., Ihm, J., Kang, J. G., Choi, M. G., Yoo, H. J., & Ihm, S. (2007) · BioFactors · doi:10.1002/biof.5520310301 · Cited by 12
“Recent evidence suggests that reactive oxygen species (ROS) mediate cell signaling in the vasculature [20].”
BackgroundOxidative stress in type 2 diabetes mellitus and methods for its correction
As, A., & Соловьева, О. Л. (2011) · Problems of Endocrinology · doi:10.14341/probl201157652-56 · Cited by 12
“Второй аспект действия ROS — индукция экспрессии ICAM-1, VCAM-1, что приводит к адгезии моноцитов, лимфоцитов на эндотелиальной стенке и к облегчению проникновения нагруженных липидами моноцитов, липидов и тромбоцитов в субэндотелиальное пространство [23].”
Qu, B., Yuan, L., Yang, L., Li, J., Lv, H., & Yang, X. (2019) · Advanced Healthcare Materials · doi:10.1002/adhm.201900582 · Cited by 12
Under Pressure: The Effect of Antioxidants on Health Consequences Related to Oxidative Stress
Patel, P. C., & Wolfe, M. T. (2020) · Entrepreneurship Theory and Practice · doi:10.1177/1042258720964184 · Cited by 12
Oseghale, O., Liong, S., Coward‐Smith, M., To, E. E., Erlich, J. R., Luong, R., Liong, F., Miles, M. A., Norouzi, S., Martin, C. M., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010703 · Cited by 12
“Oxidative stress, which is characterised by the over production of reactive oxygen species (ROS) and superoxide anions, promotes endothelial dysfunction in vascular diseases [34,35].”
BackgroundVisualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging
Gustafsson, H., Hallbeck, M., Lindgren, M., Kolbun, N., Jonson, M., Engström, M., de Muinck, E. D., & Zachrisson, H. (2014) · Magnetic Resonance in Medicine · doi:10.1002/mrm.25267 · Cited by 12
“It is well known that ROS are involved in the pathology of a large number of diseases (3), and it has been shown that oxidative stress is a key factor in the initiation and progression of atherosclerosis (4) in the development of endothelial dysfunction (5) and hypertension (6).”
BackgroundPautasso, E. J., Koretzky, M., Marcón, L., Borrego, C. S., Panini, J., & Lerman, J. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.04.202 · Cited by 12
(1→3)-β-d-Glucan inhibits a dual mechanism of peroxynitrite stroke
Saluk, J., Królewska‐Golińska, K., & Wachowicz, B. (2011) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2011.01.010 · Cited by 11
Zhang, Y., Zhou, H., Yang, J., He, Y. T., Chen, X., Nishinari, K., Wan, H., & Wan, H. (2016) · Chinese Journal of Integrative Medicine · doi:10.1007/s11655-016-2498-x · Cited by 12
Rapid and Repeatable Redox Cycling of an Insoluble Dietary Antioxidant: Electrochemical Analysis
Lee, M. E., Kim, E., Liu, Y., March, J. C., Bentley, W. E., & Payne, G. F. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf503479d · Cited by 12
Narasimhulu, C. A., Litvinov, D. Y., Sengupta, B., Jones, D., Sai‐Sudhakar, C., Firstenberg, M. S., Sun, B., & Parthasarathy, S. (2016) · Physiological Reports · doi:10.14814/phy2.12726 · Cited by 12
“Oxidative stress plays a significant role in the pathogenesis of several cardiovascular diseases, including heart failure (HF) (Griendling and Fitzgerald 2003; Madamanchi et al. 2005; Mueller et al. 2005).”
BackgroundUltrasonic transducer-guided electrochemical impedance spectroscopy to assess lipid-laden plaques
Ma, J., Luo, Y., Packard, R. R. S., Ma, T., Ding, Y., Abiri, P., Tai, Y., Zhou, Q., Shung, K. K., Li, R., et al. (2016) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2016.04.179 · Cited by 12
Relationship between calculated total antioxidant status and atherosclerotic coronary artery disease
Anvari, M. S., Babaki, M. M., Boroumand, M. A., Eslami, B., Jalali, A., & Goodarzynejad, H. (2015) · The Anatolian Journal of Cardiology · doi:10.5152/anatoljcardiol.2015.6482 · Cited by 12
“Because cigarette smoking, renal function, and diabetes mellitus are important conditions of increased oxidative stress that should be addressed (34, 35), multiple logistic regression models were established to compare outcome variables across groups, with the presence of other covariates, to find the independent effe…”
MethodHaładyj, E., Paradowska‐Gorycka, A., Felis‐Giemza, A., & Olesińska, M. (2016) · Reumatologia/Rheumatology · doi:10.5114/reum.2016.62473 · Cited by 12
“Pro-caspase-1/ NLRP3 inflammasome complexes activate caspase-1 to proteolytically cleave pro-IL-1β (35 kDa) into the bioactive cytokine IL-1β (17 kDa) [14].”
BackgroundInfluentialde Vos, L. C., Boersema, J., Hillebrands, J., Schalkwijk, C., Meerwaldt, R., Breek, J. C., Smit, A. J., Zeebregts, C. J., & Lefrandt, J. D. (2017) · BMJ Open · doi:10.1136/bmjopen-2016-012584 · Cited by 12
Zelzer, S., Enko, D., Pilz, S., Tomaschitz, A., März, W., & Meinitzer, A. (2017) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2017.03.013 · Cited by 12
Stiff Substrates Enhance Endothelial Oxidative Stress in Response to Protein Kinase C Activation
Urbano, R. L., Swaminathan, S., & Clyne, A. M. (2019) · Applied Bionics and Biomechanics · doi:10.1155/2019/6578492 · Cited by 12
“Oxidative stress and more specifically the enzyme responsible for superoxide production, NADPH oxidase, have been implicated in cardiovascular disease and atherosclerosis in particular [44, 45].”
BackgroundSasaki, M., Mitsutake, Y., Ueno, T., Fukami, A., Sasaki, K., Yokoyama, S., Ohtsuka, M., Nakayoshi, T., Itaya, N., Chibana, H., et al. (2019) · Journal of Cardiology · doi:10.1016/j.jjcc.2019.07.015 · Cited by 12
Pasala, P. K., Madhuri, D., Reddy, L. S. S., Reddy, Y. D., Somasekhar, G., Mulukuri, N. V. L. S., Nagaraju, K., Shouib, M. S., & Rizwaan, A. S. (2021) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2021.05.044 · Cited by 12
“It is well understood that oxidative metabolism is necessary for brain survival, but it is also correlated with the production of reactive oxygen species (Madamanchi et al., 2005; Schreibelt et al., 2007; Zhao et al., 2018).”
BackgroundProteomic analysis of endothelial progenitor cells exposed to oxidative stress
Liu, Y., Wei, J., Chang, M., Liu, Z., Li, D., Hu, S., & Hu, L. (2013) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2013.1419 · Cited by 12
“Increased oxidative stress impairs endothelial function and mediates atherosclerosis, stroke, cardiovascular diseases and numerous other vascular diseases (11-13).”
Noblitt, S. D., Huehls, A. M., & Morris, D. L. (2006) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2006.11.014 · Cited by 12
Radhakrishnan, G., Suzuki, R., Maeda, H., Yamamoto, M., Hirose, N., Katare, R., Lee, G.-H., Hayashi, Y., Rao, P., & Sasaguri, S. (2008) · Circulation Journal · doi:10.1253/circj.72.800 · Cited by 12
Mitochondria‐Targeted AIE Materials for Oxidative Stress‐Mediated Cancer Therapy and Beyond
Hao, N., Chen, B., Wei, X., Bao, Y., Zhang, R., Chen, P., Liu, J., Gao, H., Tu, R., & Chen, C. (2025) · Aggregate · doi:10.1002/agt2.70196 · Cited by 12
The Oxidative Balance Orchestrates the Main Keystones of the Functional Activity of Cardiomyocytes
Bevere, M., Morabito, C., Mariggiò, M. A., & Guarnieri, S. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/7714542 · Cited by 13
“There are considerable experimental findings that demonstrate the oxidative stress which can lead to several cardiovascular diseases [72].”
Boakye, E., Uddin+, S. M. I., Osuji, N., Meinert, J. L., Obisesan, O. H., Mirbolouk, M., Tasdighi, E., Shahawy, O. E., Erhabor, J., Osei, A. D., et al. (2023) · Tobacco Induced Diseases · doi:10.18332/tid/162327 · Cited by 11
Extracellular peroxiredoxin 5 exacerbates atherosclerosis via the TLR4/MyD88 pathway
Kweon, H. Y., Song, E. J., Jeong, S., Lee, S. N., Sonn, S., Seo, S., Jin, J., Kim, S., Kim, T. K., Moon, S. H., et al. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.119052 · Cited by 11
Mitochondria‑derived peptides: Promising microproteins in cardiovascular diseases (Review)
Ran, Y., Guo, Z.-L., Zhang, L., Li, H., Zhang, X.-Y., Guan, X.-M., Cui, X.-D., Chen, H., & Cheng, M. (2025) · Molecular Medicine Reports · doi:10.3892/mmr.2025.13492 · Cited by 11
Metadata
- Authors
- Madamanchi, N. R., Vendrov, A., & Runge, M. S.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2005-01
- Volume
- 25
- Issue
- 1
- Pages
- 29-38
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- 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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