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<p>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 <sup>137</sup>Cs-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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月18日

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  • Roksana Zakharyan,
  • Siras Hakobyan,
  • Agnieszka Brojakowska,
  • Suren Davitavyan,
  • Ani Stepanyan,
  • Tamara Sirunyan,
  • Gisane Khachatryan,
  • Mary K. Khlgatian,
  • Malik Bisserier,
  • Shihong Zhang,
  • Susmita Sahoo,
  • Lahouaria Hadri,
  • Venkata Naga Srikanth Garikipati,
  • Arsen Arakelyan,
  • David A. Goukassian

摘要

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.