| 研究課題/領域番号 |
23K16310
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分58020:衛生学および公衆衛生学分野関連:実験系を含む
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| 研究機関 | 自治医科大学 |
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研究代表者 |
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| 研究期間 (年度) |
2023-04-01 – 2026-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
3,640千円 (直接経費: 2,800千円、間接経費: 840千円)
2025年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円)
2024年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円)
2023年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
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| キーワード | arsenic / renin angiotensin system / HUVECs / Nrf2 / Arsenic / Endothelial dysfunction / Hypertension |
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| 研究開始時の研究の概要 |
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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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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