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 ((1)H; 0.5 Gy, 1 GeV) and iron ion ((56)Fe; 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 (56)Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56)Fe 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. 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.
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America; Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yan
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America.
authors.forename: Sharath P
authors.initials: SP
authors.lastname: Sasi
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America.
authors.forename: Hannah
authors.initials: H
authors.lastname: Gee
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America; Calhoun Cardiology Center, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
authors.forename: JuYong
authors.initials: J
authors.lastname: Lee
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America.
authors.forename: Yongyao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Steward Carney Hospital, Dorchester, Massachusetts, United States of America.
authors.forename: Raman
authors.initials: R
authors.lastname: Mehrzad
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America.
authors.forename: Jillian
authors.initials: J
authors.lastname: Onufrak
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America.
authors.forename: Jin
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
authors.forename: Heiko
authors.initials: H
authors.lastname: Enderling
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America.
authors.forename: Akhil
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America.
authors.forename: Layla
authors.initials: L
authors.lastname: Rahimi
authors.affiliation: Tufts University School of Medicine, Boston, Massachusetts, United States of America; Steward Carney Hospital, Dorchester, Massachusetts, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Morgan
authors.affiliation: Biosciences Department, Brookhaven National Laboratory, Upton, New York, United States of America.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Wilson
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America; Tufts University School of Medicine, Boston, Massachusetts, United States of America; Steward St. Elizabeth's Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carrozza
authors.affiliation: Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.affiliation: Feinberg Cardiovascular Institute, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Raj
authors.initials: R
authors.lastname: Kishore
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, Massachusetts, United States of America; Tufts University School of Medicine, Boston, Massachusetts, United States of America; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Goukassian
mesh_terms: D000208:Acute Disease; D000818:Animals; D018480:Astronauts; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology / Q000528:radiation effects*; D006334:Heart Function Tests; D006801:Humans; D007504:Iron Radioisotopes / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D011522:Protons / Q000009:adverse effects*; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D012306:Risk; D013026:Space Flight; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D007504:Iron Radioisotopes; D011522:Protons