{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:41:19Z","timestamp":1793911279226,"version":"4.8.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","funder":[{"name":"National Key Grant from Chinses Ministry of Science and Technology","award":["2016YFA0501800"],"award-info":[{"award-number":["2016YFA0501800"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870297"],"award-info":[{"award-number":["81870297"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773562"],"award-info":[{"award-number":["81773562"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and technology innovation talents of Henan Provincial Education Department","award":["19IRTSHN001"],"award-info":[{"award-number":["19IRTSHN001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1904156"],"award-info":[{"award-number":["U1904156"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2021,7,23]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale:<\/jats:title>\n                    <jats:p>Histone LSD1 (lysine-specific demethylase 1) is an important epigenetic antitumor drug target, whose inhibitors are currently in phase I\/II clinical trials. However, the potential side effects of LSD1 inhibition in the progress of cardiac remodeling to heart failure remain to be investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To evaluate the roles of myofibroblast- or cardiomyocyte-specific LSD1 deficiency in pressure overload-induced cardiac remodeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>Adult mouse cardiac fibroblasts, neonatal rat cardiac myocytes, and fibroblasts were isolated, respectively. The myofibroblast-specific and cardiomyocyte-specific LSD1 inducible knockout mice were then generated. We found that LSD1 was increased not only in human dilated cardiomyopathy hearts but also in wild-type mouse heart homogenates and isolated cardiac fibroblasts, following 20 weeks of transverse aortic constriction. The upregulation of LSD1 was also observed in Ang II-treated neonatal rat cardiac fibroblasts, which was reversed by LSD1 silence or its activity inhibition by ORY-1001. These findings suggested a potential involvement of LSD1 in cardiac remodeling. Importantly, myofibroblast-specific LSD1 inducible knockout in vivo significantly alleviated systolic dysfunction, cardiac hypertrophy, and fibrosis, following 6 and 20 weeks of transverse aortic constriction. Mechanistically, through RNA-sequencing and the following Western blot analysis, we found that loss of LSD1 in Ang II-induced myofibroblasts not only inhibited the intracellular upregulation of TGF\u03b21 (transforming growth factor \u03b21), its downstream effectors Smad2\/3 phosphorylation, as well as the phosphorylation of p38, ERK1\/2 and JNK, but also reduced the supernatant TGF\u03b21 secretion, which then decreased myocyte hypertrophy in the indirect coculture model. On the other hand, cardiomyocyte-specific LSD1-inducible knockout in vivo triggered the reprogramming of fetal genes, mild cardiac hypertrophy, and dysfunction under both basal and stressed conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our findings, for the first time, implicate that myofibroblast-specific LSD1 deletion attenuates transverse aortic constriction-induced cardiac remodeling and improves heart function, suggesting that LSD1 is a potential therapeutic target for late-stage heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.120.318149","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T05:03:09Z","timestamp":1622696589000},"page":"400-413","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Myofibroblast Deficiency of LSD1 Alleviates TAC-Induced Heart Failure"],"prefix":"10.1161","volume":"129","author":[{"given":"Jin-Ling","family":"Huo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University (J.-L.H., L.J., Q.A., X.C., Y.Q., B.W., Y.Z., X.S., H.-M.L., C.W., W.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lemin","family":"Jiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University (J.-L.H., L.J., Q.A., X.C., Y.Q., B.W., Y.Z., X.S., H.-M.L., C.W., W.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"An","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University (J.-L.H., L.J., Q.A., X.C., Y.Q., B.W., Y.Z., X.S., H.-M.L., C.W., W.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuying","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University (J.-L.H., L.J., Q.A., X.C., Y.Q., B.W., Y.Z., X.S., H.-M.L., C.W., W.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuruo","family":"Qi","sequence":"additional","affiliation":[{"name":"State Key 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School of Pharmaceutical Sciences, Zhengzhou University (J.-L.H., L.J., Q.A., X.C., Y.Q., B.W., Y.Z., X.S., H.-M.L., C.W., W.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Esophageal Cancer Prevention and Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University (J.-L.H., L.J., Q.A., X.C., Y.Q., B.W., Y.Z., X.S., H.-M.L., C.W., W.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (E.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Min","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Esophageal Cancer Prevention and 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