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Irradiation of the kidneys causes pathologic remodeling in the nontargeted heart: A role for the immune system

Journal Article · · Geography and Sustainability
 [1];  [2];  [3];  [1];  [4];  [1];  [1];  [1];  [1]
  1. Medical College of Wisconsin, Milwaukee, WI (United States)
  2. Georgetown Univ., Washington, DC (United States)
  3. Medical College of Georgia, Augusta, GA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
+ Show Author Affiliations
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.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
Greater Milwaukee Foundation; National Aeronautical and Space Administration (NASA); National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1826902
Journal Information:
Geography and Sustainability, Journal Name: Geography and Sustainability Journal Issue: 12 Vol. 2; ISSN 2573-9832
Publisher:
Elsevier; Beijing Normal UniversityCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

60 APPLIED LIFE SCIENCES
Fibrosis
T lymphocytes
X-rays
cytokines
heart diseases
hypertension
rats