Abstract Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that ⁵⁶Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE–/– mouse model in which we previously demonstrated the pro-atherogenic effect of ⁵⁶Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6Gy ⁵⁶Fe. The mice were then fed a normal diet and housed under standard conditions. At 4–5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following ⁵⁶Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

Highlights • Terrestrial radiation increases the risk of atherosclerosis in humans and mice. • We showed earlier that heavy ion radiation also increases atherogenesis (in mice). • Here we examine early vasoreactivity changes, which might predict plaque formation. • Young ApoE–/– mice were exposed to ⁵⁶Fe and vasoreactivity changes were measured. • Vasoreactivity was impaired by ⁵⁶Fe eight weeks before increased plaque formation.