Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

TitleAcceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2015
AuthorsMancuso, Mariateresa, Pasquali Emanuela, Braga-Tanaka Ignacia, Tanaka Satoshi, Pannicelli Alessandro, Giardullo Paola, Pazzaglia Simonetta, Tapio Soile, Atkinson Michael J., and Saran Anna
Date Published2015 Oct 13
KeywordsAnimals, Aorta, Thoracic, Aortic Diseases, Apolipoproteins E, atherosclerosis, Disease Progression, Dose-Response Relationship, Radiation, Female, Linear Models, Mice, Inbred C57BL, Mice, Knockout, Plaque, Atherosclerotic, Radiation Dosage, Radiation Injuries, Experimental, Risk assessment, Time Factors

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.

Alternate JournalOncotarget
PubMed ID26359350
PubMed Central IDPMC4741603