Impact of Intracellular Quality Control in Heart Failure by Selective Endoplasmic Reticulum Degradation of ER-Phagy
Project/Area Number |
19K17572
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | Fukushima Medical University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 心不全 / 細胞内品質管理 / オートファジー / 小胞体 / 品質管理 |
Outline of Research at the Start |
心不全におけるERファジーの病態意義について解明することを目的とする。分子生物学的および顕微鏡的アプローチによりERファジーを視覚化して解析する。ERファジー不全における不良タンパク質の特徴を同定し、不良タンパク質の蓄積が心筋障害から心不全の病態へと関与するのかを明らかにする。
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Outline of Final Research Achievements |
Recently, the existence of autophagy-mediated selective endoplasmic reticulum degradation (ER-phagy) has been demonstrated, but its role in the heart has not been investigated. In failing hearts 4 weeks after transverse aortic constriction, the accumulation of ubiquitin-positive proteins, P62-positive proteins, and defective proteins was suggested. mRNA levels of ER-phagy-related molecule X were significantly decreased in failing hearts after aortic constriction, suggesting that it is involved in the development of heart failure, but its functional significance needs further investigation. Besides, mass spectrometry analysis suggested that myristoylation of autophagy-related proteins is associated with ER-phagy, which is expected to be a novel mechanism.
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Academic Significance and Societal Importance of the Research Achievements |
心不全の病態において不良なタンパク質の蓄積が役割を果たしていることから、心不全の発症と進展を防ぐために心筋細胞内の恒常性維持機構としてのERファジーが新しい治療ターゲットと期待されている。本研究により、オートファジーに関連するタンパク質のミリストイル化がERファジーに関連することが示唆され、これが新規メカニズムであることが明らかになった。本研究成果からERファジーに関わる新規分子機構の可能性が明らかとなり、心不全に対する新たな治療戦略となり得ると期待され、今後の検討が必要である。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Decreases in hepatokine Fetuin-A levels are associated with hepatic hypoperfusion and predict cardiac outcomes in patients with heart failure.2022
Author(s)
Tomita Y, Misaka T*, Yoshihisa A, Ichijo Y, Ishibashi S, Matsuda M, Yamadera Y, Ohara H, Sugawara Y, Hotsuki Y, Watanabe K, Anzai F, Sato Y, Sato T, Oikawa M, Kobayashi A, Takeishi Y
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Journal Title
Clin Res Cardiol 2022 (in press).
Volume: in press
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Increases in hepatokine Selenoprotein P levels are associated with hepatic hypoperfusion and predict adverse prognosis in patients with heart failure.2022
Author(s)
Takeishi R, Misaka T*, Ichijo Y, Ishibashi S, Matsuda M, Yamadera Y, Ohara H, Sugawara Y, Hotsuki Y, Watanabe K, Anzai F, Sato Y, Sato T, Oikawa M, Kobayashi A, Yamaki T, Nakazato N, Yoshihisa A, Takeishi Y
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Journal Title
J Am Heart Assoc 2022 (in press).
Volume: in press
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Clinical impact of sleep-disordered breathing on very short-term blood pressure variability determined by pulse transit time.2020
Author(s)
Misaka T, Niimura Y, Yoshihisa A, Wada K, Kimishima Y, Yokokawa T, Abe S, Oikawa M, Kaneshiro T, Kobayashi A, Yamaki T, Kunii H, Takeishi Y.
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Journal Title
J Hypertens
Volume: 38
Issue: 9
Pages: 1703-1711
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Plasma levels of melatonin in dilated cardiomyopathy2019
Author(s)
Misaka Tomofumi、Yoshihisa Akiomi、Yokokawa Tetsuro、Sato Takamasa、Oikawa Masayoshi、Kobayashi Atsushi、Yamaki Takayoshi、Sugimoto Koichi、Kunii Hiroyuki、Nakazato Kazuhiko、Takeishi Yasuchika
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Journal Title
Journal of Pineal Research
Volume: 66
Issue: 4
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Effects of CPAP on very short-term blood pressure variability associated with sleep-disordered breathing determined by pulse-transit-time-based blood pressure measurements.2022
Author(s)
6.Misaka T, Yoshihisa A, Ohara H, Sugawara Y, Tomita Y, Tani T, Ichimura S, Watanabe K, Wada K, Abe S, Sato T, Kaneshiro T, Oikawa M, Kobayashi A, Takeishi Y.
Organizer
第86回 日本循環器学会学術集会
Related Report
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[Presentation] An ultrasound image of spleen shear wave elastography predicts adverse outcomes in heart failure patients.2021
Author(s)
Misaka T, Yoshihisa A, Ichijo Y, Sugawara Y, Ohara H, Hotsuki Y, Watanabe K, Sato Y, Oikawa M, Kobayashi A, Takeishi Y
Organizer
American Heart Association Scientific Sessions 2021
Related Report
Int'l Joint Research
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[Presentation] Hepatokine selenoprotein P is associated with hepatic hypoperfusion and predicts adverse prognosis in heart failure patients2021
Author(s)
Misaka T, Ichijo Y, Yoshihisa A, Hotsuki Y, Watanabe K, Anzai F, Sato Y, Kimishima Y, Yokokawa T, Oikawa M, Kobayashi A, Takeishi Y.
Organizer
第85回 日本循環器学会学術集会
Related Report
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[Presentation] Serum hepatokine selenoprotein P is upregulated by hepatic hypoperfusion and predicts adverse prognosis in heart failure patients.2020
Author(s)
Misaka T, Ichijo Y, Yoshihisa A, Hotsuki Y, Watanabe K, Sato Y, Kimishima Y, Yokokawa T, Oikawa M, Kobayashi A, Takeishi Y.
Organizer
American Heart Association Scientific Session 2020
Related Report
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[Presentation] Clinical implications of intrarenal hemodynamic evaluation by ultrasonography in patients with heart failure.2019
Author(s)
Misaka T, Yoshihisa A, Ichijo Y, Kimishima Y, Kanno Y, Yokokawa T, Abe S, Sato T, Oikawa M, Kobayashi A, Yamaki T, Kunii H, Nakazato K, Ishida T, Takeishi Y
Organizer
Scientific Sessions of American Heart Association 2019
Related Report
Int'l Joint Research
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