2018 Fiscal Year Research-status Report
低線量・低線量率放射線被曝による心血管疾患誘発の機構解明
| Project/Area Number |
18K18194
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| Research Institution | Hiroshima University |
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Principal Investigator |
ZAHARIEVA ELENA 広島大学, 原爆放射線医科学研究所, 特任助教 (30766697)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | cardiovascular disease / low dose rate radiation / low dose radiation / chronic inflammation / inflammatory cytokines / monocyte adhesion / adhesion molecules |
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| Outline of Annual Research Achievements |
The response of vascular cells to irradiation under acute and chronic conditions was compared by analyzing the secretion of inflammatory cytokines, cells surface expression of adhesion molecules and affinity to adhere inflammatory blood cells. Radiation doses between 0.1 Gy and 4 Gy, and dose rates between 0.07 mGy/min and 0.7 mGy/min were interrogated.
The results suggest that aortic vascular cells are sensitive to low dose/low dose rate gamma radiation. Irradiated cells responded with an upregulated inflammatory status, the functional expression of which was an increased number of adherent monocytes.
Interleukin-6, Interleukin-8 and Monocyte Chemoattractant Protein-1, as well as Intercellular Adhesion Molecule-1, appeared to be major players in radiation-induced chronic inflammation.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The project is progressing mostly according to expectations. In the first year a big part of the effort and time was devoted to establishing techniques, sample preparation, and validating protocols. Certain validation procedures, such as establishing standard curves, proved to be time-consuming but are necessary to ensure the quality of future experimental results.
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| Strategy for Future Research Activity |
In the next stage of this project the role of some critical inflammatory pathways, such as the NF-kB pathway, will be examined in human and mouse heart cells, under conditions of acute and chronic gamma-irradiation. The role of ICAM-1 in radiation-induced chronic inflammation will be further investigated by siRNA experiments.
The different steps of the monocyte adhesion cascade will be interrogated to determine which of them is most sensitive to low dose/low dose rate radiation. For the purpose, we will employ a system allowing dynamic simulation of blood flow in combination with a high-throughput imaging system.
A more comprehensive analysis of inflammatory soluble proteins will be performed by measuring a set of more than 20 cytokines and chemokines by Cytometric Bead Array analysis.
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| Causes of Carryover |
Some of the experiments planned for the next fiscal year are more expensive than initially anticipated. Also, sufficient time and effort during the last fiscal year was dedicated to establishing protocols, resulting in a small delay of the main sequence of experiments.
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Research Products
(2 results)
