{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:36:51Z","timestamp":1785771411904,"version":"3.56.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,12,19]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Cardiac hypertrophy (CH) is a well\u2010established risk factor for many cardiovascular diseases and a primary cause of mortality and morbidity among older adults. Currently, no pharmacological interventions have been specifically tailored to treat CH. OTUD7B (ovarian tumor domain\u2010containing 7B) is a member of the\u00a0ovarian tumor\u2010related protease (OTU)\u00a0family that regulates many important cell signaling pathways. However, the role of OTUD7B in the development of CH is unclear. Therefore, we investigated the role of OTUD7B in CH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">OTUD7B knockout mice were used to assay the role of OTUD7B in CH after transverse aortic coarctation surgery. We further assayed the specific functions of OTUD7B in isolated neonatal rat cardiomyocytes. We found that OTUD7B expression decreased in hypertrophic mice hearts and phenylephrine\u2010stimulated neonatal rat cardiomyocytes. Furthermore, OTUD7B deficiency exacerbated transverse aortic coarctation surgery\u2010induced myocardial hypertrophy, abnormal cardiac function, and fibrosis. In cardiac myocytes, OTUD7B knockdown promoted phenylephrine stimulation\u2010induced myocardial hypertrophy, whereas OTUD7B overexpression had the opposite effect. An immunoprecipitation\u2013mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Kr\u00fcppel\u2010like factor 4). Additional molecular experiments showed that OTUD7B impedes KLF4 degradation by inhibiting lysine residue at 48 site\u2010linked ubiquitination and suppressing myocardial hypertrophy by activating the serine\/threonine kinase pathway.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These results demonstrate that the OTUD7B\u2010KLF4 axis is a novel molecular target for CH treatment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.029745","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T12:04:09Z","timestamp":1702382649000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Ovarian Tumor Domain\u2010Containing 7B Attenuates Pathological Cardiac Hypertrophy by Inhibiting Ubiquitination and Degradation of Kr\u00fcppel\u2010Like Factor 4"],"prefix":"10.1161","volume":"12","author":[{"given":"Bin\u2010Bin","family":"Du","sequence":"first","affiliation":[{"name":"Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie\u2010Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling\u2010Yao","family":"Kong","sequence":"additional","affiliation":[{"name":"Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010Ting","family":"Shi","sequence":"additional","affiliation":[{"name":"Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian\u2010Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0561-3298","authenticated-orcid":false,"given":"Chun\u2010Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou 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