Sex-specific differences in long-term gamma and simGCRsim-associated alterations in deferential gene expression in the heart tissue

Space radiation (IR) from Solar Particle Events (SPE) and Galactic Cosmic Rays (GCR), also known as high charge and energy (HZE) IR, is a primary risk associated with deep-space missions. There are limited animal and human studies on the risk of cardiovascular disease (CVD) development due to space-IR. The cardiac effects induced by space-type IR, specifically simplified GCR simulated (simGCRsim)-IR, are yet to be discovered. We hypothesized that gamma (γ) and simGCRsim IR-induced biological responses are chronic, IR type-dependent, and may increase the relative risk for developing CVD during and after long-duration space missions. Further, we hypothesize that there may be sex-specific differences in IR-associated alterations in CV function and structure. To test our hypotheses, we exposed 3-month-old male and female age-matched C57Bl/6J wild-type (WT) mice to 137Cs-γ-IR at 100 cGy, 0.662 MeV and simGCRsim-IR at 50 cGy 500 MeV/n. We assessed cardiac function by transthoracic echocardiography (ECHO) at 28 days, and 12, 16, 22/18.5 (male/female)-months post-IR. To evaluate sex-associated differences in the regulation of the transcriptional landscape, total RNA isolated from male and female LV hearts was sequenced with Illumina NGS. Sequenced reads were splice-aligned to the mm10 mouse reference genome using the STAR aligner. Raw read counts were normalized with the DESeq2 R package and converted to log2 CPM values. Differential expression analysis and downstream bioinformatics analysis were performed using the oposSOM R package.