Abstract
Radiation exposure such as A-bomb or radiation therapy is considered a major health-risk factor for cardiovascular disease. In order to understand the molecular mechanisms underlying the inflammatory reaction frequently encountered in the vascular system after exposure to ionizing radiation, we carried out a global scale microarray and computational gene expression analyses on human umbilical endothelial cells (HUVECs) exposed to X-ray (2.5Gy). The gene ontology analysis revealed that the down-regulated genes were associated with cell cycle regulation, whereas the up-regulated genes were associated with inflammatory responses, in particular, the type 1 interferon response. The computational analysis using ingenuity pathway analysis also identified a gene network containing the interferon response factor 7 (IRF7) and its transcriptional targets such as interferon-induced transcripts (IFITs) and Mx1, which have been known to be associated with inflammation in endothelial cells. The up-regulated genes and the gene network identified here may explain the inflammatory response induced by X-irradiation. These findings uncover part of the molecular basis of the mechanism(s) of the inflammatory disorder in response to X-irradiation in HUVECs. The dataset is publicly available at the Gene Expression Omnibus (GEO) repository (http://www.ncbi.nlm.nih.gov/geo/) with accession number GSE76484.
Highlights
The association of radiation with cardiovascular disease mortality in the life span study cohort of 86,000 A-bomb survivors with estimated doses was reported [1]
Endothelial cells are known to be highly sensitive to ionizing radiation and we showed the down-regulation of eNOS expression in rabbit ear central artery 1–4 weeks after X-irradiation at a relatively high dose (45 Gy) [6], probably due to the damage of endothelial cells
For better understanding the molecular mechanisms underlying the inflammatory reaction frequently encountered in vascular system after exposure to ionizing radiation, we carried out global scale microarray and computational gene expression analyses in Human umbilical vein endothelial cells (HUVECs) after X-irradiation by 2.5 Gy, which is similar to the dose for a fraction frequently used in clinical cancer treatment
Summary
The association of radiation with cardiovascular disease mortality in the life span study cohort of 86,000 A-bomb survivors with estimated doses was reported [1]. The mechanisms by which the X-irradiation affects inflammatory response in HUVECs appear to be complex; it remains to be further elucidated. For better understanding the molecular mechanisms underlying the inflammatory reaction frequently encountered in vascular system after exposure to ionizing radiation, we carried out global scale microarray and computational gene expression analyses in HUVECs after X-irradiation by 2.5 Gy, which is similar to the dose for a fraction frequently used in clinical cancer treatment. We focused on gene response associated with inflammation in HUVECs, in particular, at an early stage after irradiation
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