This pilot study examined the long-term effects of simulated space radiation (NASA's SimGCRSim mixed galactic cosmic ray field at 50 cGy and gamma radiation at 400 cGy) on endothelial integrity and atherosclerotic plaque development in ApoE-deficient mice sacrificed at 16 months of age — more than one year post-irradiation.
Both radiation types significantly reduced luminal CD31+ and VE-cadherin+ endothelial coverage and eNOS expression in aortic root plaques compared with sham controls. Gamma irradiation significantly increased atherosclerotic plaque area; SimGCRSim showed a similar trend reaching only borderline significance. No significant differences were found in plaque lipid content, fibrotic area, necrotic core, or inflammatory cell infiltration (CD45+/CD68+), though a non-significant ~2-fold increase in plaque calcification was seen in the SimGCRSim group.
- Pilot study with small groups; SimGCRSim plaque area increase reached only borderline significance, limiting conclusions about atherosclerosis promotion. - Gamma (400 cGy) and SimGCRSim (50 cGy) doses differ substantially, making direct comparison of radiation-type effects difficult. - ApoE-null mice on normal chow are a surrogate model; mechanistic pathways were not explored.
Deep-space radiation may cause lasting vascular endothelial damage and accelerate atherosclerosis well beyond one year after exposure, supporting the need for cardiovascular monitoring and countermeasure development for astronauts on long-duration missions. These findings are currently preclinical and require human validation before clinical translation.
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