| Project/Area Number |
23K16310
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 58020:Hygiene and public health-related: including laboratory approach
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2023-04-01 – 2026-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2025: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | arsenic / renin angiotensin system / HUVECs / Nrf2 / Arsenic / Endothelial dysfunction / Hypertension |
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| Outline of Research at the Start |
Now, it is evident that low concentration and chronic arsenic exposure induced hypertension and cardiovascular diseases. In preliminary cell culture experiments, we observed that arsenic-induced endothelial dysfunction was associated with the renin-angiotensin system. Arsenic also induces endothelial dysfunction by generating excessive reactive oxygen species and by disrupting the antioxidant defense in the biological system. The proposed study aims to clarify the regulatory role of ACE2 and its interaction with Nrf2 in arsenic-induced endothelial dysfunction using experimental studies.
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| Outline of Annual Research Achievements |
Now, it is evident that low concentration and chronic arsenic exposure induced hypertension and cardiovascular diseases. In preliminary cell culture experiments, we observed that arsenic-induced endothelial dysfunction was associated with the renin-angiotensin system (RAS). Arsenic also induces endothelial dysfunction by generating excessive reactive oxygen species (ROS) and by disrupting the antioxidant defense in the biological system. Nrf2 is an antioxidant promoter protein that may play a vital role as a defensive factor against arsenic-induced endothelial dysfunction by boosting antioxidant defense systems. However, there is no comprehensive study that can explain the roles of Nrf2 in arsenic-induced endothelial dysfunction. The proposed study aims to clarify the regulatory role of RAS and its interaction with Nrf2 in arsenic-induced endothelial dysfunction using experimental and epidemiological studies. The findings will contribute to the development of the proper molecular targets in the prevention of arsenic-induced cardiovascular diseases.
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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
In the first year (2023) of the current research project, we started culturing HUVECs and tried to establish the siNrf2 model in HUVECs. We have also used sulforaphane as the Nrf2 activator agent in the HUVEC culture. We checked repeatedly the cell viability and efficiency of the siRNA Nrf2 and activation of Nrf2 in HUVECs. To check the efficiency of the Nrf2 knockdown and activation, we used western blot as well as RT-PCR laboratory techniques. Hopefully, we will continue the experiment and start exposing HUVECs (both siNrf2 and Nrf2 activated cells) to arsenic in the current and upcoming years.
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| Strategy for Future Research Activity |
In recent and upcoming years, we will perform experiments to explore the relationship between renin angiotensin systems (RAS) and reactive oxygen species (ROS) levels in arsenic-exposed HUVECs. ROS production will be checked using a fluorescent plate reader. Gene and/or protein expression associated with RAS and endothelial dysfunction will be checked using RT-PCR/western blot analysis.
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