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低剂量辐射通过改变正常和糖尿病条件下基因表达影响人主动脉内皮细胞心血管疾病风险。

Low-Dose Radiation Affects Cardiovascular Disease Risk in Human Aortic Endothelial Cells by Altering Gene Expression under Normal and Diabetic Conditions.

机构信息

Divisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea.

New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea.

出版信息

Int J Mol Sci. 2022 Aug 2;23(15):8577. doi: 10.3390/ijms23158577.

Abstract

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.

摘要

高剂量的电离辐射会导致心血管疾病(CVD);然而,<100mGy 辐射对 CVD 的影响仍报道较少。内皮细胞(ECs)在心血管健康和疾病中发挥着重要作用,其功能会因慢性疾病、代谢紊乱和吸烟等刺激而降低。然而,在糖尿病和非糖尿病状态下,低剂量辐射是否会导致 EC 中类似的分子机制受到破坏,在很大程度上尚不清楚;我们旨在通过对源自 2 型糖尿病患者的原代人主动脉内皮细胞(T2D-HAECs)和正常 HAECs 进行分子和功能表征来填补这一知识空白,以低剂量辐射作出反应。为了解决这些限制,我们对暴露于 100mGy 电离辐射后的 HAECs 和 T2D-HAECs 进行了 RNA 测序,并研究了与低剂量辐射相关的转录组变化。与未辐照组相比,低剂量照射在 HAECs 中诱导了 243 个差异表达基因(DEGs)(133 个下调和 110 个上调),在 T2D-HAECs 中诱导了 378 个 DEGs(195 个下调和 183 个上调)。我们还发现 DEGs 与干扰素(IFN)-I 信号通路之间存在显著关联,该通路通过京都基因与基因组百科全书(KEGG)通路分析、蛋白质-蛋白质网络分析和模块分析与 CVD 相关。我们的研究结果表明,低剂量辐射对与 CVD 风险相关的 EC 功能有潜在影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a1/9369411/9d6d4a5fabbe/ijms-23-08577-g001.jpg

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