Acceleration of atherogenesis in ApoE

Mariateresa Mancuso, Emanuela Pasquali, Ignacia Braga-Tanaka, Satoshi Tanaka, Alessandro Pannicelli, Paola Giardullo, Simonetta Pazzaglia, Soile Tapio, Michael J. Atkinson, Anna Saran

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21 Citations (Scopus)


There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/-mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/-females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response.
Original languageEnglish
Pages (from-to)31263 - 31271
Number of pages9
Issue number31
Publication statusPublished - 2015
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Mancuso, M., Pasquali, E., Braga-Tanaka, I., Tanaka, S., Pannicelli, A., Giardullo, P., Pazzaglia, S., Tapio, S., Atkinson, M. J., & Saran, A. (2015). Acceleration of atherogenesis in ApoE. Oncotarget, 6(31), 31263 - 31271.