Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension

YE, ZHE

doi:10.1161/JAHA.123.032828

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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

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2024DM0704.pdf (33.3 MB)

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学位論文 / Thesis or Dissertation(1)

公開日

2024-07-30

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

eng

キーワード

言語

主題Scheme

Other

主題

aldosterone

キーワード

言語

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Other

主題

cardiac fibrosis

キーワード

言語

主題Scheme

Other

主題

mineralocorticoid receptor

キーワード

言語

主題Scheme

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主題

myosin light chain

キーワード

言語

主題Scheme

Other

主題

phosphorylation

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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

open access

アクセス権URI

http://purl.org/coar/access_right/c_abf2

著者

YE, ZHE

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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本文/Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan

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内容記述

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発行日 2024-07-17

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2024-07-30 05:01:31.415482

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Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension

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