Long-term Pathway Activation in Cardiac Ventricular Tissues after Gamma and simGCRsim Irradiation

Area of Science:

• Cardiovascular Science
• Space Medicine
• Molecular Biology

Background:

• Space radiation poses risks to astronaut cardiovascular health.
• Long-term effects on heart function, particularly pathway deregulation, are not well understood.
• Previous studies noted transcriptional changes in cardiac tissues post-irradiation.

Purpose of the Study:

• To investigate long-term pathway activity alterations in cardiac tissues after space radiation exposure.
• To identify sex- and ventricle-specific differences in response to radiation.
• To compare the effects of gamma radiation and simulated galactic cosmic rays on cardiac pathways.

Main Methods:

• Applied the Pathway Signal Flow (PSF) algorithm to RNA sequencing data from mouse cardiac tissues.
• Analyzed data 440 days post-exposure to gamma rays (100 cGy) or simulated Galactic Cosmic Rays (simGCRsim, 50 cGy).
• Assessed pathway activity changes, considering sex and ventricular differences (left vs. right).

Main Results:

• Observed significant sex- and ventricle-specific pathway deregulation.
• Female left ventricles showed broad alterations in immune, cytoskeletal, and survival pathways (NF-κB, VEGF, MAPK) after simGCRsim.
• Male right ventricles had higher deregulation in PPAR, NF-κB, and HIF-1 pathways, suggesting metabolic disruption.
• simGCRsim induced more long-term pathway perturbations than gamma rays.

Conclusions:

• Sex-dependent and ventricle-specific signaling alterations contribute to long-term cardiovascular risks from space radiation.
• VEGF and NF-κB signaling are key regulators of cardiac adaptation in females.
• Further research is needed to refine cardiovascular risk assessments for space travel.