{"created":"2024-07-30T04:28:30.453805+00:00","id":2000846,"links":{},"metadata":{"_buckets":{"deposit":"a7af7567-072c-4087-8f20-e83d3422ccee"},"_deposit":{"created_by":15,"id":"2000846","owner":"15","owners":[15],"pid":{"revision_id":0,"type":"depid","value":"2000846"},"status":"published"},"_oai":{"id":"oai:mie-u.repo.nii.ac.jp:02000846","sets":["334:608:618:1721969789237"]},"author_link":[],"control_number":"2000846","item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2024-07-17","bibliographicIssueDateType":"Issued"}}]},"item_7_date_granted_59":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2024-07-17"}]},"item_7_degree_grantor_57":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"三重大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"14101","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_7_degree_name_56":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_7_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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.\nMETHODS 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.\nCONCLUSIONS: 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.","subitem_description_type":"Abstract"}]},"item_7_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"本文/Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan","subitem_description_type":"Other"},{"subitem_description":"24p","subitem_description_type":"Other"}]},"item_7_dissertation_number_60":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲医学第2270号"}]},"item_7_full_name_2":{"attribute_name":"著者（ヨミ）","attribute_value_mlt":[{"names":[{"name":"イー, ジャー","nameLang":"ja-Kana"}]}]},"item_7_publisher_30":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"三重大学"}]},"item_7_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1161/JAHA.123.032828","subitem_relation_type_select":"DOI"}}]},"item_7_text_31":{"attribute_name":"出版者（ヨミ）","attribute_value_mlt":[{"subitem_text_value":"ミエダイガク"}]},"item_7_text_63":{"attribute_name":"ノート","attribute_value_mlt":[{"subitem_text_value":"Journal of the American Heart Associationに掲載"}]},"item_7_text_65":{"attribute_name":"資源タイプ（三重大）","attribute_value_mlt":[{"subitem_text_value":"Doctoral Dissertation / 博士論文"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"YE, ZHE","creatorNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-07-30"}],"filename":"2024DM0704.pdf","filesize":[{"value":"33.3 MB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"2024DM0704.pdf","objectType":"fulltext","url":"https://mie-u.repo.nii.ac.jp/record/2000846/files/2024DM0704.pdf"},"version_id":"f03702fa-5ce3-40d1-835e-8a8fb925aeea"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"aldosterone","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"cardiac fibrosis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"mineralocorticoid receptor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"myosin light chain","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"phosphorylation","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension","subitem_title_language":"en"}]},"item_type_id":"7","owner":"15","path":["1721969789237"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-07-30"},"publish_date":"2024-07-30","publish_status":"0","recid":"2000846","relation_version_is_last":true,"title":["Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension"],"weko_creator_id":"15","weko_shared_id":-1},"updated":"2024-07-30T06:11:05.439139+00:00"}