Long-lasting sex-specific alteration in left ventricular cardiac transcriptome following gamma and simGCRsim radiation

Space irradiation (IR) is an important health risk for deep-space missions. We reported heart failure with preserved ejection fraction like cardiac phenotype 660-days following exposure to a single-dose of a simplified galactic cosmic ray simulation (simGCRsim) only in males with functional and structural impairment in left ventricular (LV) function. This sex-based dichotomy prompted us to investigate sex-specific changes in the LV transcriptome in three-month-old male and female mice exposed to ¹³⁷Cs-γ- or simGCRsim-IR. Non-IR male and female (10 each) mice served as controls. LVs were collected at 440/660- and 440/550-days post-IR, male and female, respectively. RNA sequencing, differential gene expression, and functional annotation were performed on tissues from 5 mice/group. Sex and post-IR time points had the greatest influence on gene expression, surpassing the IR-type effects. SimGCRsim-IR showed more persistent transcriptome changes than γ-IR. We suggest that the single IR effects can persist up to 550–660 days, with overwhelmingly sex-biased responses at individual gene expression level.