{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:48:17Z","timestamp":1788353297856,"version":"build-2803163510"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,11,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cardiac hypertrophy (CH) is a physiological response that compensates for blood pressure overload. Under pathological conditions, hypertrophy can progress to heart failure as a consequence of the disorganized growth of cardiomyocytes and cardiac tissue. USP10 (ubiquitin\u2010specific protease 10) is a member of the ubiquitin\u2010specific protease family of cysteine proteases, which are involved in viral infection, oxidative stress, lipid drop formation, and heat shock. However, the role of USP10 in CH remains largely unclear. Here, we investigated the roles of USP10 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\">Cardiac\u2010specific USP10 knockout (USP10\u2010CKO) mice and USP10\u2010transgenic (USP10\u2010TG) mice were used to examined the role of USP10 in CH following aortic banding. The specific functions of USP10 were further examined in isolated cardiomyocytes. USP10 expression was increased in murine hypertrophic hearts following aortic banding and in isolated cardiomyocytes in response to hypertrophic agonist. Mice deficient in USP10 in the heart exhibited exaggerated cardiac hypertrophy and fibrosis following pressure overload stress, which resulted in worsening of cardiac contractile function. In contrast, cardiac overexpression of USP10 protected against pressure overload\u2010induced maladaptive CH. Mechanistically, we demonstrated that USP10 activation and interaction with Sirt6 in response to angiotensin II led to a marked increase in the ubiquitination of Sirt6 and resulted in Akt signaling downregulation and attenuation of cardiomyocyte hypertrophy. Accordingly, inactivation of USP10 reduced Sirt6 abundance and stability and diminished Sirt6\u2010induced downstream signaling in cardiomyocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">USP10 functions as a Sirt6 deubiquitinase that induces cardiac myocyte hypertrophy and triggers maladaptive CH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.120.017751","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T10:52:47Z","timestamp":1605005567000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Deubiquitinase Ubiquitin\u2010Specific Protease 10 Deficiency Regulates Sirt6 signaling and Exacerbates Cardiac Hypertrophy"],"prefix":"10.1161","volume":"9","author":[{"given":"Dian\u2010Hong","family":"Zhang","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":"Zhen","family":"Huang","sequence":"additional","affiliation":[{"name":"Cardiovascular Hospital the First Affiliated Hospital of Zhengzhou University Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei\u2010Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"Cardiovascular Hospital the First Affiliated Hospital of Zhengzhou University Zhengzhou 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