Heavy-ion (56Fe) irradiation leads to impaired aortic relaxation prior to atherosclerotic plaque formation in ApoE-/- mice

Abstract

Terrestrial radiation exposure is a well-established risk factor for cardiovascular disease. For example, coronary artery disease and stroke are both well-established adverse effects of therapeutic radiation, especially for breast and head-and-neck cancers [ 1]. Similarly, atomic bomb survivors were significantly more likely to die of cardiovascular disease than their countrymen [ 2]. Even radiation technologists, prior to 1950 (when regulations governing shielding and occupational exposure were less rigorous), had an increased risk of clinically significant atherosclerosis [ 3]. Although the character of the radiation in interplanetary space is very different from that encountered on Earth, there is concern that exposure to this cosmic radiation might pose a similar risk for astronauts. Decreased endothelium-dependent vasodilation is thought to predispose humans to the development of structural vascular changes that precede development of atherosclerosis. Therefore, in this study, we examined the effect of 56Fe, an important component of cosmic radiation, on vascular relaxation. At the NASA Space Radiation Laboratory at Brookhaven National Laboratory, 10-week-old apoE−/− mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe, a dose in the range that was shown previously to accelerate the development of atherosclerotic plaques in this mouse model at 13 weeks post-exposure [ 4]. The mice were then transferred to the University of Alabama at Birmingham, where they were housed under standard conditions and fed a normal diet. At 4–5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation in irradiated mice was compared with that of age-matched controls from un-irradiated apoE mice and from un-irradiated wild-type mice of the same C57BL/6 genetic background. Aortic relaxation was not significantly different between un-irradiated apoE−/− mice and un-irradiated wild-type C57BL/6 mice, consistent with previous studies. 56Fe radiation, however, resulted in significantly impaired relaxation in response to acetylcholine. This suggests that heavy-ion radiation exposure leads to impairment of normal vascular reactivity prior to the appearance of atherosclerotic plaques, suggesting that it may be a driving force, rather than a consequence, of radiation-induced accelerated atherosclerosis.