Department of Radiation Biology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Department of Radiation Biology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, China; Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan Province 410078, China.
Biochim Biophys Acta Mol Basis Dis. 2024 Oct;1870(7):167443. doi: 10.1016/j.bbadis.2024.167443. Epub 2024 Jul 25.
Atherosclerosis (AS) is the most prevalent cardiovascular disease, with an exceptionally high burden. High-fat diet (HFD) is a popular diet behavior, whereas low-dose radiation (LDR) is an environmental physical factor. There is evidence to suggest that an HFD may exacerbate the onset of atherosclerosis. Whether the combination effect of HFD and LDR would have potential on atherosclerosis development remains incompletely unclear.
In this study, ApoE mice were used as atherosclerosis model animals to investigate the combination effects of HFD and LDR (10 × 0.01Gy, or 20 × 0.01Gy) on vascular lesions. Doppler ultrasound imaging, H&E staining, oil red O staining, western blotting, and immunohistochemistry (IHC) were used to assess the pro-atherosclerotic effects. LC-MS was used to detect the non-targeted lipidomic.
Long-term exposure of low-dose radiation at an accumulated dose of 0.2Gy significantly increased the occurrence of vascular stiffness and the aortic lesion in ApoE mice. The synergistic effect of HFD and LDR was observed in the development of atherosclerosis, which might be linked to both the dysbiosis of lipid metabolism and the stimulation of the inflammatory signaling system. Moreover, LDR but not HFD can activate the cGAS-STING signaling through increasing the yield of cytosolic mitochondrial DNAs as well as the expression of cGAS protein. The activation of cGAS-STING signal triggers the release of IFN-α/-β, which functions as an inflammatory amplifier in the formation of atherosclerotic plaque.
The current study offers fresh insights into the risks and mechanism that underlie the development of atherosclerosis by LDR, and there is a combination effect of LDR and HFD with the involvement of cGAS-STING signal pathway.
动脉粥样硬化（AS）是最常见的心血管疾病，具有极高的负担。高脂肪饮食（HFD）是一种流行的饮食行为，而低剂量辐射（LDR）是一种环境物理因素。有证据表明，HFD 可能会加重动脉粥样硬化的发生。HFD 和 LDR 的联合作用是否对动脉粥样硬化发展有潜在影响尚不完全清楚。
本研究以 ApoE 小鼠作为动脉粥样硬化模型动物，探讨 HFD 和 LDR（10×0.01Gy 或 20×0.01Gy）联合作用对血管病变的影响。采用多普勒超声成像、H&E 染色、油红 O 染色、Western blot 和免疫组织化学（IHC）检测促动脉粥样硬化作用。采用 LC-MS 检测非靶向脂质组学。
长期低剂量辐射（累积剂量 0.2Gy）显著增加 ApoE 小鼠血管僵硬和主动脉病变的发生。HFD 和 LDR 的协同作用在动脉粥样硬化的发生中起作用，这可能与脂质代谢失调和炎症信号系统的刺激有关。此外，LDR 而不是 HFD 可以通过增加细胞溶质线粒体 DNA 的产量和 cGAS 蛋白的表达来激活 cGAS-STING 信号。cGAS-STING 信号的激活触发 IFN-α/-β 的释放，在动脉粥样硬化斑块的形成中作为炎症放大器发挥作用。
本研究为 LDR 引发动脉粥样硬化的风险和机制提供了新的见解，并且 LDR 与 HFD 存在联合作用，涉及 cGAS-STING 信号通路。
