{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T21:11:51Z","timestamp":1766869911711,"version":"3.37.0"},"reference-count":18,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Project of Jiangxi Provincial Health Commission","award":["202210022"],"award-info":[{"award-number":["202210022"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec030\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>Pathological cardiac hypertrophy plays a significant role in the development and progression of heart failure (HF). LIM Domain Containing 1 (LIMD1) serves as a crucial regulatory factor in protein-protein interactions during cellular signal transduction. This study aims to investigate the specific roles and mechanisms of LIMD1 in pathological cardiac remodeling.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec031\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We employed an adeno-associated virus 9 (AAV9) system to overexpress LIMD1 in the hearts through tail vein injection. C57BL\/6 mice underwent transverse aortic constriction (TAC) for four weeks. Cardiac function was assessed using echocardiography, while cardiac remodeling was evaluated through histopathology and molecular techniques.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec032\">\n<jats:title>Results<\/jats:title>\n<jats:p>Our findings demonstrated elevated levels of LIMD1 in murine hearts subjected to TAC treatment and H9c2 cells challenged with angiotensin II (Ang II). Compared with wild-type (WT) mice, those injected with AAV-9-LIMD1 exhibited significantly reduced TAC-induced cardiac dysfunction, hypertrophy, and fibrosis. Mechanistically, both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments suggested that the beneficial effects of LIMD1 might be associated with the inhibition of the YAP1\/AKT\/GSK3\u03b2 signaling pathway.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec033\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In summary, this study is the first to demonstrate the protective effects of LIMD1 against TAC-induced pathological cardiac remodeling. These effects are attributed to the inhibition of the YAP1\/AKT\/GSK3\u03b2 signaling pathway.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0316149","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T18:43:25Z","timestamp":1739385805000},"page":"e0316149","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Upregulated LIMD1 alleviates pressure overload-induced cardiac hypertrophy via inhibits YAP1\/AKT\/GSK3\u03b2 signaling"],"prefix":"10.1371","volume":"20","author":[{"given":"Fengwen","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liru","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingmei","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9604-7601","authenticated-orcid":true,"given":"Quan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"issue":"1","key":"pone.0316149.ref001","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nrcardio.2016.163","article-title":"Neurohormonal 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chronic mechanical stress overload","volume":"12","author":"P Yue","year":"2022","journal-title":"Theranostics"},{"key":"pone.0316149.ref005","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1161\/CIRCRESAHA.115.306624","article-title":"miR-206 mediates YAP-induced cardiac hypertrophy and survival","volume":"117","author":"Y Yang","year":"2015","journal-title":"Circ Res"},{"key":"pone.0316149.ref006","doi-asserted-by":"crossref","first-page":"109198","DOI":"10.1016\/j.abb.2022.109198","article-title":"YAP1 induces hyperglycemic stress-mediated cardiac hypertrophy and fibrosis in an AKT-FOXM1 dependent signaling pathway","volume":"722","author":"A Mondal","year":"2022","journal-title":"Arch Biochem Biophys"},{"issue":"7","key":"pone.0316149.ref007","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cub.2010.02.035","article-title":"Ajuba LIM proteins are negative regulators of the Hippo signaling pathway","volume":"20","author":"M Das Thakur","year":"2010","journal-title":"Curr Biol"},{"issue":"5","key":"pone.0316149.ref008","doi-asserted-by":"crossref","first-page":"jcs214700","DOI":"10.1242\/jcs.214700","article-title":"Tension-dependent regulation of mammalian Hippo signaling through LIMD1","volume":"131","author":"C Ibar","year":"2018","journal-title":"J Cell Sci"},{"key":"pone.0316149.ref009","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.2147\/CMAR.S174856","article-title":"LIMD1 is a survival prognostic marker of gastric cancer and hinders tumor progression by suppressing activation of YAP1","volume":"10","author":"D Zhang","year":"2018","journal-title":"Cancer Manag Res"},{"key":"pone.0316149.ref010","first-page":"8347759","article-title":"Upregulation of biomarker Limd1 was correlated with immune infiltration in doxorubicin-related cardiotoxicity","author":"R Zhang","year":"2023","journal-title":"Mediators 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