{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T03:23:46Z","timestamp":1785381826035,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,12]],"date-time":"2020-12-12T00:00:00Z","timestamp":1607731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:p>Hypoxia\u2010induced apoptosis is linked to the pathogenesis of myocardial infarction (MI) and heart failure. Ubiquitin\u2010specific peptidase 7 (USP7) is related to catabolic\/pro\u2010apoptotic signaling. However, its role in cardiomyocyte injury is unclear. In this study, we aimed to investigate the role and the underlying regulatory mechanism of USP7 in MI. H9c2 cardiomyocytes were cultured in hypoxia to establish an <jats:italic>in vitro<\/jats:italic> model of myocardial hypoxic\/ischemic injury. Sprague\u2010Dawley (SD) rats were used to establish animal models with MI. Quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) and Western blot assays were performed to evaluate the expression levels of miR\u2010409\u20105p, USP7, and p53, respectively. After USP7 and miR\u2010409\u20105p were selectively regulated in H9c2 cells, the inflammatory response, apoptosis, and cell viability were detected by ELISA, flow cytometry, and MTT assay, respectively. The interaction between USP7 and miR\u2010409\u20105p was determined by bioinformatics analysis, qRT\u2010PCR, Western blot, and dual\u2010luciferase reporter assay. LVEF, LVIDd, and LVIDs of rats after MI were also measured. USP7 expression was markedly elevated while miR\u2010409\u20105p expression was significantly down\u2010regulated in H9c2 cells under hypoxic culture. Augmentation of USP7 expression led to a dramatic promotion of hypoxia\u2010induced apoptosis of cardiomyocytes, accompanied by an increase in the secretion of the cytokines IL\u20101\u03b2, TNF\u2010\u03b1, and IL\u20106. Myocardial injury markers LDH, cTnI, and CK\u2010MB expressions were also increased. Besides, overexpression of USP7 aggravated left ventricular remodeling and decreased left ventricular function of the rats. Conversely, the up\u2010regulation of miR\u2010409\u20105p expression protected H9c2 cells from apoptosis and inhibited the release of cytokines and myocardial injury. Left ventricular remodeling and left ventricular function were also improved by miR\u2010409\u20105p overexpression. Furthermore, USP7 was identified as a target of miR\u2010409\u20105p and the overexpression of miR\u2010409\u20105p reversed the effects of USP7 on H9c2 cells. USP7 exacerbates myocardial ischemic injury by promoting inflammation and apoptosis of cardiomyocytes, and the up\u2010regulation of its expression is partly caused by the down\u2010regulation of miR\u2010409\u20105p expression.<\/jats:p>","DOI":"10.1111\/apm.13100","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T13:27:54Z","timestamp":1606397274000},"page":"152-162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["USP7, negatively regulated by miR\u2010409\u20105p, aggravates hypoxia\u2010induced cardiomyocyte injury"],"prefix":"10.1111","volume":"129","author":[{"given":"Qiang","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Cardiology Yanan Hospital of Kunming Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Yanan 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