Chronic radiation exposure aggravates atherosclerosis by stimulating neutrophil infiltration

Abstract

Background

Radiation exposure is known to increase the risk of chronic inflammatory diseases, such as atherosclerosis, by modulating inflammation.

Methods

To investigate the infiltration of leukocytes in radiation-aggravated atherosclerosis, we examined low-density lipoprotein receptor-deficient (Ldlr–/–) mice and C57BL/6j mice after exposure to 0.5 or 1 Gy radiation over 16 weeks.

Results

We found that radiation exposure induced atherosclerosis development in Ldlr–/– mice, as demonstrated by increased lipid-laden plaque size, reactive oxygen species levels, and levels of the pro-inflammatory cytokines, IL-1β and TNF-α, in the aortas and spleens. Total plasma cholesterol, triglyceride, and LDL cholesterol levels were also increased by radiation exposure, along with cardiovascular risk. We also showed dose-dependent increases in neutrophils and monocytes that coincided with a reduction in lymphocytes in the spleens of Ldlr–/– mice. The correlation between the infiltration of leukocytes and cytokine production was also confirmed in the hearts and spleens of these mice.

Conclusions

We concluded that chronic radiation exposure increased the production of pro-inflammatory mediators, which was associated with the migration of neutrophils and inflammatory monocytes into sites of atherosclerosis. Thus, our data suggest that the accumulation of neutrophils and inflammatory monocytes, together with the reduction of lymphocytes, contribute to aggravated atherosclerosis in Ldlr–/– mice under prolonged exposure to radiation.

Keywords:

• Atherosclerosis
• radiation
• Ldlr–/– mouse
• neutrophil infiltration

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This research was funded by the National Research Foundation of Korea (NRF) Grants funded by the Korea Government (MSIT), Grant Number (No. NRF2019R1A2C208741612 and No. NRF2019R1F1A105994012).

Notes on contributors

You Yeon Choi

You Yeon Choi is a Post-Doctor in National Radiation Emergency Medical Center. She is currently studying the radiation effects on atherosclerosis at low doses using a model mouse and cytogenetic and biochemical methods to examine the exposed level to radiation from human blood.

Areumnuri Kim

Areumnuri Kim is a Senior Researcher in National Radiation Emergency Medical Center. She has investigated to explain hematological response of ionizing radiation after radiotherapy and explored the immunological response in the radiation-induced intestinal damage.

Ki Moon Seong

Ki Moon Seong is a Senior Researcher in National Radiation Emergency Medical Center. His research interest is the biological effects of radiation exposure at low doses in daily life and biodosimetry on the people exposed to radiation. Currently, he contributes to the collaborating works of UNSCEAR as a Korean delegate.