Proteomic Remodeling in the Female Heart During Spaceflight and Recovery

Spaceflight profoundly impacts cardiovascular physiology. To gain insight into the underlying molecular adaptations, we examined the female cardiac proteome during spaceflight and recovery. We hypothesized that spaceflight remodels the cardiac proteome, including mitochondrial bioenergetics and redox homeostasis pathways, during both flight and recovery, altering cardiovascular health risk. Proteomic analysis was performed on hearts from female C57BL/6J mice flown aboard the International Space Station (ISS) for 55 to 60 days as part of the NASA Rodent Research-20 (RR-20) study and a recovery cohort returned to Earth after 42 days, with sampling occurring five days after landing, and corresponding ground controls. Consistent with our hypothesis, spaceflight enriched mitochondrial bioenergetic pathways relative to ground controls, including cellular respiration, the tricarboxylic acid cycle, and oxidative phosphorylation. These changes occurred alongside the remodeling of antioxidant pathways, suggesting altered redox regulation during flight and increased susceptibility to reactive oxygen species (ROS) accumulation in the heart versus controls. Postflight recovery was characterized by distinct metabolic, redox, and structural remodeling signatures, including pathways associated with sarcomere organization, contractile function, and extracellular matrix regulation. These findings reveal cardiac proteomic remodeling during and after spaceflight and provide molecular insights relevant to cardiovascular risk assessment and countermeasure development for exploration missions.