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Effects of Low and Moderate Dose of total body X-ray Irradiation on Abdominal Aortic Aneurysms in a Murine Model
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International audience. Exposure to ionizing radiation has been linked to cardiovascular diseases, although the relationship between low doses of radiation and circulatory diseases remains uncertain. Some studies suggest that chronic low dose rate ionizing radiation may have a protective effect on atherosclerosis. The development of abdominal aortic aneurysms (AAAs) is a complex process involving genetic, environmental, and biomechanical factors. In this study, we investigate the impact of low to moderate doses of ionizing radiation on AAAs in mice and explore potential underlying mechanisms through in vitro studies.We used a model of male ApoE-/- mice (B6.129P2 background) at the age of 10-12 weeks. Mice were implanted with a subcutaneous mini-osmotic pump filled with a solution of angiotensin II (25 mg/mL in saline solution) to perfuse at 1000 ng/kg/min during 7 or 28 days. Mice received X-ray total body irradiation with a single dose of either 50 mGy or 1000 mGy, either (i) 3 days before, (ii) 1 day after, or (iii) 3 days after the Angiotensin II infusion. In addition, we irradiated primary smooth muscle cells isolated from male C57BL6/J mice aged less than 10 weeks, which were cultured and irradiated with a single dose of either 50 mGy or 1000 mGy, either with or without angiotensin II supplementation.Our results showed that the effects of radiation were highly dependent on the timing of exposure and the dose administered. At the lower dose of 50 mGy, we did not observe any significant effects of irradiation, regardless of the timing of exposure. However, at the higher dose of 1000 mGy, we observed a significant decrease in aortic aneurysm dilatation and incidence of the pathology compared to non-irradiated group. Additionally, at 1000 mGy, we observed a significant decrease in actin content in the media of the aortic wall without apoptosis, as well as an increase in adventitial thickness and the number of cells present compared to non-irradiated mice.Our findings suggest that the effects of ionizing radiation on aortic aneurysm are dependant to the dose and physipathological context at the time of irradiation. Indeed, the timing of the irradiation relative to the angiotensin II infusion appears to play a significant role. In vitro studies may shed light on the mechanisms underlying the observed effects of radiation exposure on the aortic wall.
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