| 研究課題/領域番号 |
22K15368
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| 研究機関 | 国立研究開発法人国立循環器病研究センター |
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研究代表者 |
Waddingham Mark 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (70822211)
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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| キーワード | Pulmonary Hypertension / Right Ventricle / Myocardium / Diastolic Dysfunction / Sarcomere / Microtubules / Heat Shock Proteins / Cardiomyocyte |
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| 研究実績の概要 |
In the first year of this proposal, I have begun developing the model of Group 2 pulmonary hypertension, using the Dahl-Iwai salt-sensitive (DIS) rat combined with a 4% NaCl diet for 12 weeks. So far we have established that when compared to the salt-resistant (DIR) control rats, DIS rats tend to develop left ventricular hypertrophy and demonstrate evidence of early diastolic dysfunction. Right ventricle (RV) catheterisation has revealed that DIS rats have slightly elevated pulmonary pressures, in particular during cardiac fluid challenge testing. Further analysis of RV diastolic function is function is currently being undertaken.
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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
The rat model of Group 2 pulmonary hypertension is currently being fully validated, however the data collected to date is very promising. It is expected that full haemodynamic characterisation will be completed by summer 2023, followed by extensive cardiomyocyte function and biochemical studies.
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| 今後の研究の推進方策 |
As mentioned above, upon completion of the validation of the group 2 pulmonary hypertension model (planned summer 2023), cardiomyocyte function and biochemical studies will begin to investigate the roles of the extracellular matrix, microtubules, saromeres and organelles in the development of RV diastolic dysfunction. This is expected to make a majority of FY2023.
In early 2024, I plan to begin investigating if boosting small heat shock proteins within the myocardium may be a useful therapeutic strategy to alleviate diastolic dysfunction of the RV in both group 1 & group 2 pulmonary hypertension.
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| 次年度使用額が生じた理由 |
Remaining funds from FY2022 will be used to support ongoing in vivo experiments as well as isolated cardiomyocyte and biochemical studies.
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