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

数据独立采集蛋白质组学揭示 C57BL/6J 小鼠接受局部高剂量心脏照射后血清中的长期生物标志物

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作者:Omid Azimzadeh, Christine von Toerne, Vikram Subramanian, Wolfgang Sievert, Gabriele Multhoff, Michael J Atkinson, Soile Tapio

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

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.

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.

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

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.

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