A single 25 Gy cardiac radiation dose improved hypertrophy, fibrosis, diastolic function, and reduced arrhythmias by restoring Ca2+ homeostasis in TnT R92Q HCM mice.
Does a single 25 Gy dose of cardiac radiation improve cardiac remodeling and electrophysiological properties in a TnT R92Q HCM mouse model?
A single 25 Gy dose of cardiac radiation attenuates hypertrophic cardiomyopathy progression and improves calcium homeostasis in a preclinical mouse model, providing mechanistic insight into the benefits of SBRT for HCM.
Abstract Background and Aims Stereotactic body radiotherapy (SBRT) delivers high-dose radiation to targeted tissues while minimizing off-target exposure. Our initial first-in man clinical study demonstrated promising outcomes of SBRT in drug-refractory hypertrophic cardiomyopathy (HCM) patients. This study aims to explore the unclear mechanisms behind these benefits. Methods The effects of a single 25 Gy dose of cardiac radiation (CR, mimicking SBRT) were investigated in the TnT R92Q HCM mouse model. Cardiac structure and function were evaluated using echocardiography. Cardiac transcriptomics, phosphoproteomics, contraction-relaxation kinetics, intracellular calcium transients, and electrophysiological properties were evaluated to investigate the effects of CR on cardiomyocyte contraction-relaxation and the underlying mechanisms. Results Twelve-weeks after CR, the HCM phenotyping was significantly improved in terms of attenuated progression of hypertrophy, fibrosis, and improved diastolic function compared to untreated TnT R92Q HCM mice. CR exhibited notable anti-arrhythmic effects, reduced ventricular electrical remodeling. These protective effects were accompanied by altered phosphorylation profiles of sarcomere and calcium-associated proteins. At cellular level, CR reduced calcium-sensitive force production, improved relaxation kinetics, and restored calcium homeostasis, which likely contributed to its anti-arrhythmic effects and mitigation of ventricular electrical remodeling in TnT R92Q HCM mice. Conclusions A single 25 Gy dose of cardiac radiation attenuates cardiac remodeling by restoring calcium sensitivity and relaxation kinetics and improving electrical propagation in TnT R92Q HCM mice.CR inhibits disease progression and redu CR rescued cardiomyocyte relaxation kine
Huang et al. (2025) studied this question. A single 25 Gy cardiac radiation dose improved hypertrophy, fibrosis, diastolic function, and reduced arrhythmias by restoring Ca2+ homeostasis in TnT R92Q HCM mice.