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Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension
http://hdl.handle.net/10076/0002000846
http://hdl.handle.net/10076/0002000846a0c29fbd-df90-46fe-b82f-7cf35ade4b9c
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
2024DM0704.pdf (33.3 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2024-07-30 | |||||||
| タイトル | ||||||||
| タイトル | Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | aldosterone | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | cardiac fibrosis | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | mineralocorticoid receptor | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | myosin light chain | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | phosphorylation | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| 著者 |
YE, ZHE
× YE, ZHE
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| 著者（ヨミ） | ||||||||
| 姓名 | イー, ジャー | |||||||
| 言語 | ja-Kana | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | BACKGROUND: Myosin phosphatase targeting subunit 2 (MYPT2) is an important subunit of cardiac MLC (myosin light chain) phosphatase, which plays a crucial role in regulating the phosphorylation of MLC to phospho-MLC (p-MLC). A recent study demonstrated mineralocorticoid receptor-related hypertension is associated with RhoA/Rho-associated kinase/MYPT1 signaling upregulation in smooth muscle cells. Our purpose is to investigate the effect of MYPT2 on cardiac function and fibrosis in mineralocorticoid receptor-related hypertension. METHODS AND RESULTS: HL-1 murine cardiomyocytes were incubated with different concentrations or durations of aldosterone. After 24-hour stimulation, aldosterone increased CTGF (connective tissue growth factor) and MYPT2 and decreased p-MLC in a dose-dependent manner. MYPT2 knockdown decreased CTGF. Cardiac-specific MYPT2-knockout (c-MYPT2−/−) mice exhibited decreased type 1 phosphatase catalytic subunit β and increased p-MLC. A disease model of mouse was induced by subcutaneous aldosterone and 8% NaCl food for 4 weeks after uninephrectomy. Blood pressure elevation and left ventricular hypertrophy were observed in both c-MYPT2−/− and MYPT2+/+ mice, with no difference in heart weights or nuclear localization of mineralocorticoid receptor in cardiomyocytes. However, c-MYPT2−/− mice had higher ejection fraction and fractional shortening on echocardiography after aldosterone treatment. Histopathology revealed less fibrosis, reduced CTGF, and increased p-MLC in c-MYPT2−/− mice. Basal global radial strain and global longitudinal strain were higher in c-MYPT2−/− than in MYPT2+/+ mice. After aldosterone treatment, both global radial strain and global longitudinal strain remained higher in c-MYPT2−/− mice compared with MYPT2+/+ mice. CONCLUSIONS: Cardiac-specific MYPT2 knockout leads to decreased myosin light chain phosphatase and increased p-MLC. MYPT2 deletion prevented cardiac fibrosis and dysfunction in a model of mineralocorticoid receptor-associated hypertension. |
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| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 本文/Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan | |||||||
| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 24p | |||||||
| 書誌情報 |
発行日 2024-07-17 |
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| DOI | ||||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | 10.1161/JAHA.123.032828 | |||||||
| フォーマット | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | application/pdf | |||||||
| 出版者 | ||||||||
| 出版者 | 三重大学 | |||||||
| 出版者（ヨミ） | ||||||||
| 値 | ミエダイガク | |||||||
| 学位名 | ||||||||
| 学位名 | 博士(医学) | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 14101 | |||||||
| 学位授与機関名 | 三重大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2024-07-17 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲医学第2270号 | |||||||
| ノート | ||||||||
| 資源タイプ（三重大） | ||||||||
| 値 | Doctoral Dissertation / 博士論文 | |||||||
