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Title: Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

Abstract

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 CVmore » 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.« less

Authors:
 [1];  [2];  [2];  [3];  [2];  [4];  [2];  [2];  [5];  [2];  [2];  [6];  [7];  [8];  [9];  [10];  [11]
+ Show Author Affiliations
  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
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE; National Aeronautics and Space Administration (NASA); National Institutes of Health (NIH)
OSTI Identifier:
1259269
Grant/Contract Number:  
NNJ10ZSA001N; 14GRNT18860032; 10GRNT4710003; NHLBI HL106098; HL091983
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 9; Journal Issue: 10; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.

Citation Formats

Yan, Xinhua, Sasi, Sharath P., Gee, Hannah, Lee, JuYong, Yang, Yongyao, Mehrzad, Raman, Onufrak, Jillian, Song, Jin, Enderling, Heiko, Agarwal, Akhil, Rahimi, Layla, Morgan, James, Wilson, Paul F., Carrozza, Joseph, Walsh, Kenneth, Kishore, Raj, and Goukassian, David A. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation. United States: N. p., 2014. Web. doi:10.1371/journal.pone.0110269.
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Yan, Xinhua, Sasi, Sharath P., Gee, Hannah, Lee, JuYong, Yang, Yongyao, Mehrzad, Raman, Onufrak, Jillian, Song, Jin, Enderling, Heiko, Agarwal, Akhil, Rahimi, Layla, Morgan, James, Wilson, Paul F., Carrozza, Joseph, Walsh, Kenneth, Kishore, Raj, & Goukassian, David A. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation. United States. https://doi.org/10.1371/journal.pone.0110269
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Yan, Xinhua, Sasi, Sharath P., Gee, Hannah, Lee, JuYong, Yang, Yongyao, Mehrzad, Raman, Onufrak, Jillian, Song, Jin, Enderling, Heiko, Agarwal, Akhil, Rahimi, Layla, Morgan, James, Wilson, Paul F., Carrozza, Joseph, Walsh, Kenneth, Kishore, Raj, and Goukassian, David A. Wed . "Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation". United States. https://doi.org/10.1371/journal.pone.0110269. https://www.osti.gov/servlets/purl/1259269.
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@article{osti_1259269,
title = {Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation},
author = {Yan, Xinhua and Sasi, Sharath P. and Gee, Hannah and Lee, JuYong and Yang, Yongyao and Mehrzad, Raman and Onufrak, Jillian and Song, Jin and Enderling, Heiko and Agarwal, Akhil and Rahimi, Layla and Morgan, James and Wilson, Paul F. and Carrozza, Joseph and Walsh, Kenneth and Kishore, Raj and Goukassian, David A.},
abstractNote = {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.},
doi = {10.1371/journal.pone.0110269},
journal = {PLoS ONE},
number = 10,
volume = 9,
place = {United States},
year = {Wed Oct 22 00:00:00 EDT 2014},
month = {Wed Oct 22 00:00:00 EDT 2014}
}
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https://doi.org/10.1371/journal.pone.0110269
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