Irradiation of the kidneys causes pathologic remodeling in the nontargeted heart: A role for the immune system. FASEB Bioadv 2020 Dec;2(12):705-719
Date
12/19/2020Pubmed ID
33336158Pubmed Central ID
PMC7734425DOI
10.1096/fba.2020-00071Scopus ID
2-s2.0-85101816410 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
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.
Author List
Lenarczyk M, Laiakis EC, Mattson DL, Johnson BD, Kronenberg A, North PE, Komorowski R, Mäder M, Baker JEAuthors
John E. Baker PhD Professor in the Surgery department at Medical College of WisconsinBryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Paula E. North MD, PhD Professor in the Pathology department at Medical College of Wisconsin
