Distinguish response of low-dose radiation with different dose-rate on gene expression of human coronary artery endothelial cells: a bioinformatic study based on transcriptomic sequencing

Abstract

Purpose

People are exposed to low-dose radiation in medical diagnosis, occupational, or life circumstances, but the effect of low-dose radiation on human health is still controversial. The biological effects of radiation below 100 mGy are still unproven. In this study, we observed the effects of low-dose radiation (100 mGy) on gene expression in human coronary artery endothelial cells (HCAECs) and its effect on molecular signaling.

Materials and methods

HCAECs were exposed to 100 mGy ionizing radiation at 6 mGy/h (low-dose-rate) or 288 mGy/h (high-dose-rate). After 72 h, total RNA was extracted from sham or irradiated cells for Quant-Seq 3'mRNA-Seq, and bioinformatic analyses were performed using Metascape. Gene profiling was validated using qPCR.

Results

Compared to the non-irradiated control group, 100 mGy of ionizing radiation at 6 mGy/h altered the expression of 194 genes involved in signaling pathways related to heart contraction, blood circulation, and cardiac myofibril assembly differentially. However, 100 mGy at 288 mGy/h altered expression of 450 genes involved in cell cycle-related signaling pathways, including cell division, nuclear division, and mitosis differentially. Additionally, gene signatures responding to low-dose radiation, including radiation dose-specific gene profiles (HIST1H2AI, RAVER1, and POTEI) and dose-rate-specific gene profiles (MYL2 for the low-dose-rate and DHRS9 and CA14 for the high-dose-rate) were also identified.

Conclusions

We demonstrated that 100 mGy low-dose radiation could alter gene expression and molecular signaling pathways at the low-dose-rate and the high-dose-rate differently. Our findings provide evidence for further research on the potential impact of low-dose radiation on cardiovascular function.

Keywords:

• Low-dose radiation
• low-dose-rate
• gene expression
• endothelial cells
• cardiovascular disease

Authors contributions

S.H.L. and H.J.L. designed the experiments. S.H.L, Y.S. K.J.C. and C.G.L. performed the molecular analyses and bioinformatic analyses. S.H.L, Y.S. and H.J.L wrote the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data and all materials are available on request from the corresponding author. RNA-seq data used in this study are deposited in the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) under the accession number of GSE261231.

Additional information

Funding

This work was supported by a grant of the National Research Foundation of Korea [NRF-2020M2C8A2069337] and [50531-2023] funded by KIRAMS.

Notes on contributors

Soo-Ho Lee

Soo-Ho Lee, M.S., is a researcher at the Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Republic of Korea.

Yeonghoon Son

Yeonghoon Son, D.V.M., Ph.D., is a senior researcher at the Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Republic of Korea.

Kyu Jin Choi

Kyu Jin Choi, Ph.D., is a senior researcher at the Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Republic of Korea.

Chang Geun Lee

Chang Geun Lee, Ph.D., is a senior researcher at the Research Center, Dongnam Institute of Radiological and Medical Sciences, Republic of Korea.

Hae-June Lee

Hae-June Lee, D.V.M., Ph.D., is a principal researcher at the Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Republic of Korea.