TRPM4 Participates in Irradiation-Induced Aortic Valve Remodeling in Mice

Thoracic radiotherapy can lead to cardiac remodeling including valvular stenosis due to fibrosis and calcification. The monovalent non-selective cation channel TRPM4 is known to be involved in calcium handling and to participate in fibroblast transition to myofibroblasts, a phenomenon observed during aortic valve stenosis. The goal of this study was to evaluate if TRPM4 is involved in irradiation-induced aortic valve damage. Four-month-old Trpm4 and Trpm4 mice received 10 Gy irradiation at the aortic valve. Cardiac parameters were evaluated by echography until 5 months post-irradiation, then hearts were collected for morphological and histological assessments. At the onset of the protocol, Trpm4 and Trpm4 mice exhibited similar maximal aortic valve jet velocity and mean pressure gradient. Five months after irradiation, Trpm4 mice exhibited a significant increase in those parameters, compared to the untreated animals while no variation was detected in Trpm4 mice. Morphological analysis revealed that irradiated Trpm4 mice exhibited a 53% significant increase in the aortic valve cusp surface while no significant variation was observed in Trpm4 animals. Collagen staining revealed aortic valve fibrosis in irradiated Trpm4 mice but not in irradiated Trpm4 animals. It indicates that TRPM4 influences irradiation-induced valvular remodeling.