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Title: Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

Journal Article · · PLoS ONE
 [1];  [2];  [2];  [3];  [2];  [4];  [2];  [2];  [5];  [2];  [2];  [6];  [7];  [8];  [9];  [10];  [11]
  1. GeneSys Research Institute, Boston, MA (United States); Tufts Univ. School of Medicine, Boston, MA (United States)
  2. GeneSys Research Institute, Boston, MA (United States)
  3. GeneSys Research Institute, Boston, MA (United States); Univ. of Connecticut Health Center, Farmington, CT (United States)
  4. Steward Carney Hospital, Dorchester, MA (United States)
  5. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States). Dept. of Integrated Mathematical Oncology
  6. Tufts Univ. School of Medicine, Boston, MA (United States); Steward Carney Hospital, Dorchester, MA (United States)
  7. Brookhaven National Lab. (BNL), Upton, NY (United States)
  8. GeneSys Research Institute, Boston, MA (United States); Tufts Univ. School of Medicine, Boston, MA (United States); Steward St. Elizabeth's Medical Center, Boston, MA (United States)
  9. Boston Univ. School of Medicine, Boston, MA (United States). Whitaker Cardiovascular Institute
  10. Northwestern Univ., Chicago, IL (United States). Feinberg Cardiovascular Institute
  11. GeneSys Research Institute, Boston, MA (United States); Tufts Univ. School of Medicine, Boston, MA (United States); Boston Univ. School of Medicine, Boston, MA (United States). Whitaker Cardiovascular Institute
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Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

Research Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE; National Aeronautics and Space Administration (NASA); National Institutes of Health (NIH)
Grant/Contract Number:
NNJ10ZSA001N; 14GRNT18860032; 10GRNT4710003; NHLBI HL106098; HL091983
OSTI ID:
1259269
Journal Information:
PLoS ONE, Vol. 9, Issue 10; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 43 works
Citation information provided by
Web of Science

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Cited By (8)

Heart in space: effect of the extraterrestrial environment on the cardiovascular system journal October 2017
Radiation-Induced Cardiovascular Disease: Mechanisms and Importance of Linear Energy Transfer journal January 2018
Effects of Iron Overload and Oxidative Damage on the Musculoskeletal System in the Space Environment: Data from Spaceflights and Ground-Based Simulation Models journal September 2018
LGM2605 Reduces Space Radiation-Induced NLRP3 Inflammasome Activation and Damage in In Vitro Lung Vascular Networks journal January 2019
GeneLab Database Analyses Suggest Long-Term Impact of Space Radiation on the Cardiovascular System by the Activation of FYN Through Reactive Oxygen Species journal February 2019
Do Apollo Astronaut Deaths Shine a Light on Deep Space Radiation and Cardiovascular Disease? journal December 2016
Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight journal October 2017
Oxidative Stress as Cause, Consequence, or Biomarker of Altered Female Reproduction and Development in the Space Environment journal November 2018

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Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.