{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:33:22Z","timestamp":1791848002680,"version":"4.3.4"},"reference-count":51,"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":[[2022,11,15]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">SENP1 (sentrin\/small ubiquitin\u2010like modifier\u2010specific protease 1) has emerged as a significant modulator involved in the pathogenesis of a variety of human diseases, especially cancer. However, the regulatory roles of SENP1 in cardiovascular biology and diseases remain controversial. Our current study aims to clarify the function and regulation of SENP1 in pressure overload\u2010induced cardiac remodeling and dysfunction.<\/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\">We used a preclinical mouse model of transverse aortic constriction coupled with in vitro studies in neonatal rat cardiomyocytes to study the role of SENP1 in cardiac hypertrophy. Gene delivery system was used to knockdown or overexpress SENP1 in vivo. Here, we observed that SENP1 expression was significantly augmented in murine hearts following transverse aortic constriction as well as neonatal rat cardiomyocytes treated with phenylephrine or angiotensin II. Cardiac\u2010specific SENP1 knockdown markedly exacerbated transverse aortic constriction\u2010induced cardiac hypertrophy, systolic dysfunction, fibrotic response, and cellular apoptosis. In contrast, adenovirus\u2010mediated SENP1 overexpression in murine myocardium significantly attenuated cardiac remodeling and dysfunction following chronic pressure overload. Mechanistically, JAK2 (Janus kinase 2) and STAT3 (signal transducer and activator of transcription 3) acted as new interacting partners of SENP1 in this process. SENP1\u2010JAK2\/STAT3 interaction suppressed STAT3 nuclear translocation and activation, ultimately inhibiting the transcription of prohypertrophic genes and the initiation of hypertrophic response. Furthermore, cardiomyocyte\u2010specific STAT3 knockout mice were generated to validate the underlying mechanisms, and the results showed that STAT3 ablation blunted the cardiac hypertrophy\u2010promoting effects of SENP1 deficiency. Additionally, pharmacological inhibition of SENP1 by Momordin Ic amplified cardiac remodeling post\u2010transverse aortic constriction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Our study provided evidence that SENP1 protected against pressure overload\u2010induced cardiac remodeling and dysfunction via inhibiting STAT3 signaling. SENP1 supplementation might constitute a new promising treatment against cardiac hypertrophy. Notably, cardiovascular side effects should be seriously considered while applying systemic SENP1 blockers to suppress tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.122.027004","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T05:38:03Z","timestamp":1668231483000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["SENP1 Protects Against Pressure Overload\u2010Induced Cardiac Remodeling and Dysfunction Via Inhibiting STAT3 Signaling"],"prefix":"10.1161","volume":"11","author":[{"given":"Dan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan PR China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases Wuhan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan PR China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases Wuhan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan PR China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases Wuhan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang\u2010Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan PR China"},{"name":"Hubei Key Laboratory of Metabolic and Chronic Diseases Wuhan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan PR China"},{"name":"Hubei Key Laboratory of Metabolic 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