Cardiovascular changes in atherosclerotic ApoE-deficient mice exposed to Co60 (γ) radiation

PLoS One. 2013 Jun 20;8(6):e65486. doi: 10.1371/journal.pone.0065486. Print 2013.

Abstract

Background: There is evidence for a role of ionizing radiation in cardiovascular diseases. The goal of this work was to identify changes in oxidative and nitrative stress pathways and the status of the endothelinergic system during progression of atherosclerosis in ApoE-deficient mice after single and repeated exposure to ionizing radiation.

Methods and results: B6.129P2-ApoE tmlUnc mice on a low-fat diet were acutely exposed (whole body) to Co60 (γ) (single dose 0, 0.5, and 2 Gy) at a dose rate of 36.32 cGy/min, or repeatedly (cumulative dose 0 and 2 Gy) at a dose-rate of 0.1 cGy/min for 5 d/wk, over a period of 4 weeks. Biological endpoints were investigated after 3-6 months of recovery post-radiation. The nitrative stress marker 3-nitrotyrosine and the vasoregulator peptides endothelin-1 and endothelin-3 in plasma were increased (p<0.05) in a dose-dependent manner 3-6 months after acute or chronic exposure to radiation. The oxidative stress marker 8-isoprostane was not affected by radiation, while plasma 8-hydroxydeoxyguanosine and L-3,4-dihydroxyphenylalanine decreased (p<0.05) after treatment. At 2Gy radiation dose, serum cholesterol was increased (p = 0.008) relative to controls. Percent lesion area increased (p = 0.005) with age of animal, but not with radiation treatment.

Conclusions: Our observations are consistent with persistent nitrative stress and activation of the endothelinergic system in ApoE-/- mice after low-level ionizing radiation exposures. These mechanisms are known factors in the progression of atherosclerosis and other cardiovascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Atherosclerosis / blood*
  • Cholesterol / blood
  • Cobalt Radioisotopes
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / blood
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Endothelins / blood
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / radiation effects*
  • Female
  • Levodopa / blood
  • Lipid Peroxidation
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Nitrites / blood
  • Oxidative Stress / radiation effects
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • Radiation Injuries, Experimental / blood*
  • Tyrosine / blood

Substances

  • Apolipoproteins E
  • Cobalt Radioisotopes
  • Endothelins
  • Nitrites
  • 8-epi-prostaglandin F2alpha
  • Tyrosine
  • Levodopa
  • 8-Hydroxy-2'-Deoxyguanosine
  • Cholesterol
  • Dinoprost
  • Deoxyguanosine

Grants and funding

The work was supported by operational funds at Health Canada and AECL (Atomic Energy of Canada Limited). Outside of the investigators directly involved in the study, the institutional funders had no direct role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.