Effects of Proton Therapy on Cardiac Fibrosis, Calcium Homeostasis, and AQP4 Expression in Hypergravity-Exposed Rats

Proton therapy is increasingly used to treat pediatric and adult brain tumors, but there is still uncertainty surrounding the biological effects of protons on the heart. Also, the molecular and functional responses to proton irradiation are still unknown. This study investigates the effect of protons on cardiac disease by comparing their effects on the hearts of rats exposed to hypergravity. A total of 20 Sprague Dawley rats were tested, including a group that was irradiated with 0.1 Gy of protons to the heart, a group exposed to hypergravity, a group exposed to both protons and hypergravity, and a control group. Changes in AQP4, calcium homeostasis, and fibrosis-related markers were investigated using Western blotting, immunohistochemistry, etc. The proton-irradiated group showed no changes compared to the control group. In rats exposed to hypergravity, the cardiac fibrosis markers TGF-ꞵ1, MMP9, and MMP2 were increased. On the other hand, the group exposed to hypergravity followed by proton irradiation tended to display a significant decrease in these markers. Along with reduced fibrosis-related markers, the consistent tendency was also confirmed in the cardiac calcium homeostasis-related proteins and AQP4 through Western blotting. In summary, our findings indicate that rats subjected to hypergravity experienced both cardiac hypertrophy and fibrosis, while proton therapy appeared to mitigate the effects of cardiac disease. These results suggest that proton therapy prevents heart disease triggered by hypergravity, providing insights for protecting astronauts' cardiovascular health.