Low-Dose Radiation Affects Cardiovascular Disease Risk in Human Aortic Endothelial Cells by Altering Gene Expression under Normal and Diabetic Conditions.
Soo-Ho LeeYe Ji JeongJeongwoo ParkHyun-Yong KimYeonghoon SonKwang Seok KimHae-June LeePublished in: International journal of molecular sciences (2022)
High doses of ionizing radiation can cause cardiovascular diseases (CVDs); however, the effects of <100 mGy radiation on CVD remain underreported. Endothelial cells (ECs) play major roles in cardiovascular health and disease, and their function is reduced by stimuli such as chronic disease, metabolic disorders, and smoking. However, whether exposure to low-dose radiation results in the disruption of similar molecular mechanisms in ECs under diabetic and non-diabetic states remains largely unknown; we aimed to address this gap in knowledge through the molecular and functional characterization of primary human aortic endothelial cells (HAECs) derived from patients with type 2 diabetes (T2D-HAECs) and normal HAECs in response to low-dose radiation. To address these limitations, we performed RNA sequencing on HAECs and T2D-HAECs following exposure to 100 mGy of ionizing radiation and examined the transcriptome changes associated with the low-dose radiation. Compared with that in the non-irradiation group, low-dose irradiation induced 243 differentially expressed genes (DEGs) (133 down-regulated and 110 up-regulated) in HAECs and 378 DEGs (195 down-regulated and 183 up-regulated) in T2D-HAECs. We also discovered a significant association between the DEGs and the interferon (IFN)-I signaling pathway, which is associated with CVD by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein network analysis, and module analysis. Our findings demonstrate the potential impact of low-dose radiation on EC functions that are related to the risk of CVD.
Keyphrases
- low dose
- endothelial cells
- high glucose
- cardiovascular disease
- high dose
- gene expression
- radiation induced
- type diabetes
- transcription factor
- protein protein
- network analysis
- aortic valve
- left ventricular
- small molecule
- vascular endothelial growth factor
- single cell
- healthcare
- dendritic cells
- heart failure
- pulmonary artery
- immune response
- wound healing
- induced pluripotent stem cells
- risk assessment
- coronary artery
- pluripotent stem cells
- cardiovascular risk factors
- cell proliferation
- pulmonary hypertension
- human health