Key result
Local kidney irradiation with 10 Gy of X-rays caused pathologic remodeling in the shielded, nontargeted heart of WAG rats after 120 days, an effect partially mediated by the immune system.
Why the study?
Cardiac disease is a frequent adverse event of radiotherapy, and identifying the mechanisms responsible for radiation-induced heart injury is needed to develop interventions.
Local kidney irradiation induces indirect pathologic cardiac remodeling in susceptible rats, mediated in part by the immune system and circulating factors.
Suggests possible cardiac monitoring needs with kidney radiotherapy; leaves open human applicability of immune-mediated bystander remodeling.
Cardiac disease is a frequent and significant adverse event associated with radiotherapy for cancer. Identifying the underlying mechanism responsible for radiation injury to the heart will allow interventions to be developed. In the present study, we tested if local kidney irradiation results in remodeling of the shielded, nontargeted heart. One kidney, two kidneys, or the total body of male WAG and Dahl SS rats were irradiated with 10 Gy of X-rays. Local kidney irradiation resulted in systemic hypertension, increased BUN, infiltration of T lymphocytes, natural killer cells, and macrophages into the renal cortex and medulla, and renal fibrosis. Local irradiation of kidneys in WAG rats resulted in remodeling in the nontargeted heart after 120 days, manifested by perivascular fibrosis and increased interventricular septal thickness, but was not seen in Dahl SS rats due to a high baseline level of fibrosis in the sham-irradiated animals. Genetic depletion of T cells mitigated the nephropathy after local kidney irradiation, indicating a role for the immune system in mediating this outcome. Local kidney irradiation resulted in a cascade of pro-inflammatory cytokines and low-molecular weight metabolites into the circulation associated with transmission of signals resulting in pathologic remodeling in the nontargeted heart. A new model is proposed whereby radiation-induced cardiac remodeling in susceptible animals is indirect, with lower hemi body organs such as the kidney exporting factors into the circulation that cause remodeling outside of the irradiated field in the shielded, nontargeted heart. This nontargeted effect appears to be mediated, in part, by the immune system.
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Lenarczyk et al. (2020) studied Radiation-induced cardiac remodeling. Local kidney irradiation vs. Sham-irradiated animals was evaluated on Pathologic remodeling in the nontargeted heart (perivascular fibrosis and increased interventricular septal thickness). Local kidney irradiation with 10 Gy of X-rays caused pathologic remodeling in the shielded, nontargeted heart of WAG rats after 120 days, an effect partially mediated by the immune system.
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