HZE56Fe-Ion Irradiation Induces Endothelial Dysfunction in Rat Aorta: Role of Xanthine Oxidase
Open accessAbstract
Ionizing radiation has been implicated in the development of significant cardiovascular complications. Since radiation exposure is associated with space exploration, astronauts are potentially at increased risk of accelerated cardiovascular disease. This study investigated the effect of high atomic number, high-energy (HZE) iron-ion radiation on vascular and endothelial function as a model of space radiation. Rats were exposed to a single whole-body dose of iron-ion radiation at doses of 0, 0.5 or 1 Gy. In vivo aortic stiffness and ex vivo aortic tension responses were measured 6 and 8 months after exposure as indicators of chronic vascular injury. Rats exposed to 1 Gy iron ions demonstrated significantly increased aortic stiffness, as measured by pulse wave velocity. Aortic rings from irradiated rats exhibited impaired endothelial-dependent relaxation consistent with endothelial dysfunction. Acute xanthine oxidase (XO) inhibition or reactive oxygen species (ROS) scavenging restored endothelial-dependent responses to normal. In addition, XO activity was significantly elevated in rat aorta 4 months after whole-body irradiation. Furthermore, XO inhibition, initiated immediately after radiation exposure and continued until euthanasia, completely inhibited radiation-dependent XO activation. ROS production was elevated after 1 Gy irradiation while production of nitric oxide (NO) was significantly impaired. XO inhibition restored NO and ROS production. Finally, dietary XO inhibition preserved normal endothelial function and vascular stiffness after radiation exposure. These results demonstrate that radiation induced XO-dependent ROS production and nitroso-redox imbalance, leading to chronic vascular dysfunction. As a result, XO is a potential target for radioprotection. Enhancing the understanding of vascular radiation injury could lead to the development of effective methods to ameliorate radiation-induced vascular damage.
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In rats exposed to high-energy and high-atomic number (HZE) iron ions as a model of space radiation, there is an increase in aortic stiffness and tension, two characteristics that coincide with endothelial dysfunction.
“It was shown that there is an increase in aortic stiffness and tension, two characteristics that coincide with the existence of endothelial dysfunction94.”
From Key points for the development of antioxidant cocktails to prevent cellular stress and damage caused by reactive oxygen species (ROS) during manned space missions (2021) · cites this paper as [94]
The study summary in our copy reports increased aortic stiffness after 1 Gy iron-ion irradiation and impaired endothelium-dependent relaxation in aortic rings, consistent with endothelial dysfunction. It says aortic tension responses were measured, but does not report an increase in tension; that part of the claim is unsupported. No section or page is identified for this passage in our copy. (LLM, conf=0.86)
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Cardiovascular effects of space radiation: implications for future human deep space exploration
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Radiation and Radiation Disorders
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Cardiovascular Effects of Cosmic Radiation and Microgravity
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Effects of Fe particle irradiation on human endothelial barrier structure and function
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Organs in orbit: how tissue chip technology benefits from microgravity, a perspective
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Ion beams for space radiation radiobiological effect studies
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Effects of Simulated 5-Ion Galactic Cosmic Radiation on Function and Structure of the Mouse Heart
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Is space flight arrhythmogenic?
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Early changes in vascular reactivity in response to 56Fe irradiation in ApoE–/– mice
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The Effects of Simulated and Real Microgravity on Vascular Smooth Muscle Cells
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Biological effects of high-LET irradiation on the circulatory system
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Radioprotective Effect of Febuxostat Against Testicular Damage Induced by Ionizing Radiation in Mice
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Mitigating Radiation Effects on Humans During Space Travel: Recent Developments
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Cosmic Radiations and the Cardiovascular System: A Narrative Review
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Heart Disease and Microgravity: The Dawn of a New Medical Era?: A Narrative Review
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Cardiovascular risks and hazards associated with deep space exploration
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The space radiation environment and human health risks
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Radiation in Space: The Biology
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Mitigating Radiation Effects on Humans During Space Travel: Recent Developments
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Human Health Risks Relevant to Deep Space Mars Exploration Missions
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Caenorhabditis elegans: a tiny model animal for space biology research
Ho, P. L., Tran, S. H., Song, D., Lee, J. I., Kim, H. S., Kwon, H. C., & Kang, K. (2025) · Applied Biological Chemistry · doi:10.1186/s13765-025-01042-5
- Authors
- Soucy, K. G., Lim, H. K., Kim, J. H., Oh, Y., Attarzadeh, D. O., Sevinc, B., Kuo, M. M., Shoukas, A. A., Vazquez, M. E., & Berkowitz, D. E.
- Affiliations
- University of Louisville (US)
- Johns Hopkins University (US)
- Brookhaven National Laboratory (US)
- Venue
- Radiation Research
- Publisher
- Radiation Research Society
- Published
- 2011-10
- Volume
- 176
- Issue
- 4
- Pages
- 474-485
- ISSN
- 0033-7587 (ISSN-L)
- 1938-5404
- OpenAlex
- W2010710541
- Cited by
- 77
- References
- 59
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 10 · 2020: 9 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 6 · 2013: 1 · 2012: 1
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.rrjournal.org
- Licence
- cc-by-nc-nd
- Locations
- Radiation Research (publishedVersion)
- PubMed (publishedVersion)
- BioOne Complete (BioOne) (submittedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Aeronautics and Space Administration
- Brookhaven National Laboratory
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Keywords
- space radiation, endothelial dysfunction, xanthine oxidase, reactive oxygen species, nitric oxide, aortic stiffness, vascular injury, endothelium-dependent relaxation, pulse wave velocity, radiation protection
- MeSH terms
- Animals, Aorta, Biomechanical Phenomena, Endothelium, Vascular, Enzyme Inhibitors, Iron, Male, Nitric Oxide, Oxypurinol, Time Factors, Whole-Body Irradiation, Xanthine Oxidase, Rats, Wistar, Reactive Oxygen Species, Rats
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