Exposure to multiple ion beams, broadly representative of galactic cosmic rays, causes perivascular cardiac fibrosis in mature male rats

Abstract

Long-duration space exploratory missions to the Earth’s moon and the planet Mars are actively being planned. Such missions will require humans to live for prolonged periods beyond low earth orbit where astronauts will be continuously exposed to high energy galactic cosmic rays (GCRs). A major unknown is the potential impact of GCRs on the risks of developing degenerative cardiovascular disease, which is a concern to NASA. A ground-based rat model has been used to provide a detailed characterization of the risk of long-term cardiovascular disease from components of GCRs at radiation doses relevant to future human missions beyond low earth orbit. Six month old male WAG/RijCmcr rats were irradiated at a ground-based charged particle accelerator facility with high energy ion beams broadly representative of GCRs: protons, silicon and iron. Irradiation was given either as a single ion beam or as a combination of three ion beams. For the doses used, the single ion beam studies did not show any significant changes in the known cardiac risk factors and no evidence of cardiovascular disease could be demonstrated. In the three ion beam study, the total cholesterol levels in the circulation increased modestly over the 270 day follow up period, and inflammatory cytokines were also increased, transiently, 30 days after irradiation. Perivascular cardiac collagen content, systolic blood pressure and the number of macrophages found in the kidney and in the heart were each increased 270 days after irradiation with 1.5 Gy of the three ion beam grouping. These findings provide evidence for a cardiac vascular pathology and indicate a possible threshold dose for perivascular cardiac fibrosis and increased systemic systolic blood pressure for complex radiation fields during the 9 month follow up period. The development of perivascular cardiac fibrosis and increased systemic systolic blood pressure occurred at a physical dose of the three ion beam grouping (1.5 Gy) that was much lower than that required to show similar outcomes in earlier studies with the same rat strain exposed to photons. Further studies with longer follow up periods may help determine whether humans exposed to lower, mission-relevant doses of GCRs will develop radiation-induced heart disease.

Effects of photon irradiation in the presence and absence of hindlimb unloading on the behavioral performance and metabolic pathways in the plasma of Fischer rats

“…The relative biologic effectiveness represents the ratio of doses required by two different irradiation types (e.g., photons and galactic cosmic radiation) to cause the same level of biologic effect. In a previous study in WAG/RijCmcr rats, the increase in perivascular collagen occurred after a much lower total dose of 1.5 Gy from a three-ion beam grouping, representative of galactic cosmic radiation, as compared with 10 Gy of photon irradiation ( Lenarczyk et al, 2023 ). The range of radiation doses in the present study was expanded to include 3, 8, and 10 Gy.…”

Irradiation and Alterations in Hippocampal DNA Methylation

“…Effects on the brain following irradiation might involve peripheral immune responses, including infiltrating neutrophils [ 9 ], the gut microbiome, and the bi-directional gut–brain axis [ 26 , 27 ]. Increasing evidence supports that X-ray and gamma irradiation are associated with epigenetic changes, including alterations in DNA methylation involving Long Interspersed Nucleotide Element 1 (LINE-1) and Alu elements [ 28 ]. Alterations in DNA methylation involving these genetic elements are also seen following simulated space radiation [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”