Abstract
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.
Highlights
It is, nowadays, commonly acknowledged that the exposure of the heart to ionizing radiation, as in radiation therapy for breast cancer, Hodgkin’s disease, or other cancers of the chest, increases the risk of heart disease [1, 2]
The analysis identified and quantified 499 proteins (Supplementary Table 1)
The expression of 42 and 59 proteins was significantly changed at 8 and 16 Gy, respectively, suggesting a dose-dependent increase in the number of significantly deregulated proteins (Table 1). The majority of these proteins (76% at 8 Gy and 83% at 16 Gy) have been previously annotated as serum proteins based on the Plasma Proteome Database (PPD)
Summary
Nowadays, commonly acknowledged that the exposure of the heart to ionizing radiation, as in radiation therapy for breast cancer, Hodgkin’s disease, or other cancers of the chest, increases the risk of heart disease [1, 2]. This has become a growing problem with the advancements in cancer therapy that have successfully reduced both mortality rates and the recurrence, expanding the life expectancy of the survivors [3, 4]. 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
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