Radiation-induced disruption of cardiac mitochondrial bioenergetics and nucleotide homeostasis in mice
Abstract
ABSTRACT:
Aims: Cardiac stereotactic body radiotherapy (SBRT) has emerged as a promising non-invasive treatment for refractory ventricular tachycardia (VT). Intriguingly, the clinical benefit of SBRT often occurs within days of treatment, preceding the development of radiation-induced fibrosis, suggesting alternative underlying mechanisms. This study aimed to investigate the acute and persistent effects of ionizing radiation on cardiac bioenergetics and mitochondrial function, providing mechanistic insights into early cardiac responses to radiation exposure.
Methods and results: We employed a translational multi-model approach, including HL-1 mouse cardiomyocytes and ex vivo mouse left ventricular living myocardial slices (LMS). Bioenergetic profiling, assessment of mitochondrial respiration and calcium handling were performed following exposure to clinically relevant radiation doses (10 Gy and 25 Gy). In HL-1 cardiomyocytes, 10 Gy induced acute bioenergetic stress, characterized by reduced adenylate energy charge, cytoskeletal disorganization, and impaired mitochondrial respiration, accompanied by increased calcium oscillation amplitude. 25 Gy exposure led to NAD + depletion but paradoxically enhanced mitochondrial respiratory capacity, suggesting an adaptive metabolic response. Murine myocardial slices demonstrated reduced creatine content while preserving energy balance as indicated by phosphocreatine/ATP ratio, indicating tissue-level metabolic resilience. These findings…
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Evidence Hub reads this as a preprint, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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