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Exposure to multiple ion beams, broadly representative of galactic cosmic rays, causes perivascular cardiac fibrosis in mature male rats

Journal Article · · PLoS ONE
 [1];  [2];  [1];  [1];  [3];  [1]
  1. Medical College of Wisconsin, Milwaukee, WI (United States)
  2. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
  3. Univ. of Oxford (United Kingdom)
Long-duration space exploratory missions to the Earth’s moon and the planet Mars are actively being planned. Such missions will require humans to live for prolonged periods beyond low earth orbit where astronauts will be continuously exposed to high energy galactic cosmic rays (GCRs). A major unknown is the potential impact of GCRs on the risks of developing degenerative cardiovascular disease, which is a concern to NASA. A ground-based rat model has been used to provide a detailed characterization of the risk of long-term cardiovascular disease from components of GCRs at radiation doses relevant to future human missions beyond low earth orbit. Six month old male WAG/RijCmcr rats were irradiated at a ground-based charged particle accelerator facility with high energy ion beams broadly representative of GCRs: protons, silicon and iron. Irradiation was given either as a single ion beam or as a combination of three ion beams. For the doses used, the single ion beam studies did not show any significant changes in the known cardiac risk factors and no evidence of cardiovascular disease could be demonstrated. In the three ion beam study, the total cholesterol levels in the circulation increased modestly over the 270 day follow up period, and inflammatory cytokines were also increased, transiently, 30 days after irradiation. Perivascular cardiac collagen content, systolic blood pressure and the number of macrophages found in the kidney and in the heart were each increased 270 days after irradiation with 1.5 Gy of the three ion beam grouping. These findings provide evidence for a cardiac vascular pathology and indicate a possible threshold dose for perivascular cardiac fibrosis and increased systemic systolic blood pressure for complex radiation fields during the 9 month follow up period. The development of perivascular cardiac fibrosis and increased systemic systolic blood pressure occurred at a physical dose of the three ion beam grouping (1.5 Gy) that was much lower than that required to show similar outcomes in earlier studies with the same rat strain exposed to photons. Further studies with longer follow up periods may help determine whether humans exposed to lower, mission-relevant doses of GCRs will develop radiation-induced heart disease.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
2470768
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 4 Vol. 18; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (51)

Radiation‐induced tissue damage and response journal February 2020
A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis journal August 1995
Inverse co-expression of EZH2 and acetylated H3K27 in prostatic tissue journal August 2022
Ground-based research with heavy ions for space radiation protection journal January 2005
Inflammatory cytokines as biomarkers in heart failure journal March 2015
Interleukin-17A stimulates cardiac fibroblast proliferation and migration via negative regulation of the dual-specificity phosphatase MKP-1/DUSP-1 journal February 2012
Inflammatory biomarkers for predicting cardiovascular disease journal October 2013
Cardiac Risks of Breast-cancer Radiotherapy: A Contemporary View journal April 2006
Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment journal September 2014
Late onset cardiovascular dysfunction in adult mice resulting from galactic cosmic ray exposure journal April 2022
Cardiac Magnetic Resonance for Early Detection of Radiation Therapy-Induced Cardiotoxicity in a Small Animal Model journal March 2021
Noninvasive Imaging of Cardiovascular Injury Related to the Treatment of Cancer journal August 2014
Overview of the NASA space radiation laboratory journal November 2016
Effects of low-dose oxygen ions and protons on cardiac function and structure in male C57BL/6J mice journal February 2019
Effects of single-dose protons or oxygen ions on function and structure of the cardiovascular system in male Long Evans rats journal August 2020
Delayed molecular responses to brain irradiation journal January 1997
Radiation as a Risk Factor for Cardiovascular Disease journal October 2011
Inflammation and cardiovascular disease mechanisms journal February 2006
An analysis of variance test for normality (complete samples) journal December 1965
Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis journal September 2013
Pathology and biology of radiation-induced cardiac disease journal September 2016
Irradiation of the kidneys causes pathologic remodeling in the nontargeted heart: A role for the immune system journal October 2020
Radiation-induced eosinophils improve cytotoxic T lymphocyte recruitment and response to immunotherapy journal January 2021
The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight journal April 2019
Arterial structure and function during and after long-duration spaceflight journal July 2020
Joint distribution of lipoprotein cholesterol classes. The Framingham study. journal May 1983
Cardiac Fibrosis journal March 2016
Inflammatory Biomarkers Interleukin‐6 and C‐Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial journal October 2017
Local Production of Interleukin-4 During Radiation-induced Pneumonitis and Pulmonary Fibrosis in Rats: Macrophages as a Prominent Source of Interleukin-4 journal September 1997
Rodent Immunohistochemistry: Pitfalls and Troubleshooting journal September 2013
Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques–pulse sequences, analysis algorithms, and applications journal January 2011
On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other journal March 1947
Late radiation response of kidney assayed by tubule-cell survival journal June 1986
A perspective on the impact of radiation therapy on the immune rheostat journal July 2017
NASA’s first ground-based Galactic Cosmic Ray Simulator: Enabling a new era in space radiobiology research journal May 2020
Circulating Interleukin-18 as a Biomarker of Total-Body Radiation Exposure in Mice, Minipigs, and Nonhuman Primates (NHP) journal October 2014
Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation journal October 2014
Serum Lipoprotein Pattern in Rats, Dogs and Monkeys, Including Method Comparison and Influence of Menstrual Cycle in Monkeys journal January 1993
Space Radiation Absorbed Dose Distribution in a Human Phantom journal January 2002
Different Sequences of Fractionated Low-Dose Proton and Single Iron-Radiation-Induced Divergent Biological Responses in the Heart journal August 2017
Age at Exposure to Radiation Determines Severity of Renal and Cardiac Disease in Rats journal May 2019
Radiation Dose Associated with Renal Failure Mortality: A Potential Pathway to Partially Explain Increased Cardiovascular Disease Mortality Observed after Whole-Body Irradiation journal December 2011
The Association Between Chronic Kidney Disease and Cardiovascular Disease Risk Factors in Atomic Bomb Survivors journal January 2013
Impact of Angiotensin II Type 2 Receptor Blockade on Experimental Radiation Nephropathy journal March 2004
Cardiac Injury after 10 Gy Total Body Irradiation: Indirect Role of Effects on Abdominal Organs journal September 2013
Sequential Evaluation of Radiation-Induced Glomerular Ultrastructural Changes in the Pig Kidney journal September 1993
10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model journal December 2009
How to Translate Time? The Temporal Aspect of Human and Rodent Biology journal March 2017
Longitudinal Trajectories of Cholesterol from Midlife through Late Life according to Apolipoprotein E Allele Status journal October 2014
T Cells Contribute to Pathological Responses in the Non-Targeted Rat Heart following Irradiation of the Kidneys journal December 2022
Cholesterol in the Prediction of Atherosclerotic Disease journal January 1979

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