{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:13:28Z","timestamp":1762866808600,"version":"3.41.2"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,2,23]]},"abstract":"<jats:sec xml:lang=\"en\"><jats:title>Background<\/jats:title><jats:p xml:lang=\"en\">Angiotensin\u2010converting enzyme 3 (<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3) is a recently defined homolog of<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>. However, the pathophysiological function of<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3 is largely unknown. Here, we aim to explore the role of<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3 in pathological cardiac hypertrophy.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Methods and Results<\/jats:title><jats:p xml:lang=\"en\">Neonatal rat cardiomyocytes (<jats:styled-content style=\"fixed-case\">NRCM<\/jats:styled-content>s) with gain and loss of function of<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3 and mice with global knockout or cardiac\u2010specific overexpression of<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3 were used in this study. In cultured cardiomyocytes,<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3 conferred protection against angiotensin<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>(Ang<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>)\u2010induced hypertrophic growth. Cardiac hypertrophy in mice was induced by aortic banding (<jats:styled-content style=\"fixed-case\">AB<\/jats:styled-content>) and the extent of hypertrophy was analyzed through echocardiographic, pathological, and molecular analyses. Our data demonstrated that<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3\u2010deficient mice exhibited more pronounced cardiac hypertrophy and fibrosis and a strong decrease in cardiac contractile function, conversely, cardiac\u2010specific<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3\u2010overexpressing mice displayed an attenuated hypertrophic phenotype, compared with control mice, respectively. Analyses of the underlying molecular mechanism revealed that<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3\u2010mediated protection against cardiac hypertrophy by suppressing the activation of mitogen\u2010activated protein kinase kinase (<jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>)\u2010regulated extracellular signal\u2010regulated protein kinase (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2) signaling, which was further evidenced by the observation that inhibition of the<jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 signaling by U0126 rescued the exacerbated hypertrophic phenotype in<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3\u2010deficient mice.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Conclusions<\/jats:title><jats:p xml:lang=\"en\">Our comprehensive analyses suggest that<jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>3 inhibits pressure overload\u2010induced cardiac hypertrophy by blocking the<jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 signaling pathway.<\/jats:p><\/jats:sec>","DOI":"10.1161\/jaha.115.002680","type":"journal-article","created":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T04:33:38Z","timestamp":1455856418000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Angiotensin\u2010Converting Enzyme 3 (ACE3) Protects Against Pressure Overload\u2010Induced Cardiac Hypertrophy"],"prefix":"10.1161","volume":"5","author":[{"given":"Chang\u2010Jiang","family":"Yu","sequence":"first","affiliation":[{"name":"Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, 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