Table_1_Data-Independent Acquisition Proteomics Reveals Long-Term Biomarkers in the Serum of C57BL/6J Mice Following Local High-Dose Heart Irradiation.XLSX

Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity.
Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA.
Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation, and cholesterol metabolism. We found significantly enhanced expression of proinflammatory cytokines (TNF-α, TGF-β, IL-1, and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low-density lipoprotein (LDL), and oxidized LDL was increased, whereas that of high-density lipoprotein was decreased by irradiation.
Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy.

背景与目的
心脏毒性是放射治疗已知的不良反应。当心脏功能出现可检测异常时，往往提示已发生晚期且多不可逆的心脏损伤。因此，早期检测心脏毒性对延缓并减轻疾病进展具有重要意义。本研究以小鼠为模型，探究局部心脏照射后长期血清蛋白质组的变化，以期筛选辐射诱导心脏毒性的生物标志物。

材料与方法
对接受8 Gy或16 Gy X射线局部心脏照射的C57BL/6J小鼠，于照射后20周采集血清样本，对照组小鼠接受假照射处理。采用基于数据非依赖性采集质谱（data-independent acquisition mass spectrometry）的定量蛋白质组学技术对样本进行检测分析，随后借助生物信息学方法与酶联免疫吸附测定（ELISA）对蛋白质组学数据开展后续研究。

结果
分析结果表明，辐射可使多种参与急性期反应、炎症过程及胆固醇代谢的血清蛋白水平发生改变。本研究发现，照射组小鼠血清中的促炎细胞因子（肿瘤坏死因子-α、转化生长因子-β、白细胞介素-1及白细胞介素-6）表达水平显著上调。游离脂肪酸、总胆固醇、低密度脂蛋白（LDL）及氧化低密度脂蛋白水平均出现升高，而高密度脂蛋白水平则因辐射照射有所下降。

结论
本研究明确了心脏照射的全身效应，并揭示了血清中的辐射指纹（radiation fingerprint），该特征谱可用于识别放射治疗后可能出现的心脏不良反应。