{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:56:38Z","timestamp":1793325398432,"version":"4.5.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2024,2,2]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disorder. However, the pathogenesis of HCM, especially its nongenetic mechanisms, remains largely unclear. Transcription factors are known to be involved in various biological processes including cell growth. We hypothesized that SP1 (specificity protein 1), the first purified TF in mammals, plays a role in the cardiomyocyte growth and cardiac hypertrophy of HCM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              Cardiac-specific conditional knockout of\n              <jats:italic toggle=\"yes\">Sp1<\/jats:italic>\n              mice were constructed to investigate the role of SP1 in the heart. The echocardiography, histochemical experiment, and transmission electron microscope were performed to analyze the cardiac phenotypes of cardiac-specific conditional knockout of\n              <jats:italic toggle=\"yes\">Sp1<\/jats:italic>\n              mice. RNA sequencing, chromatin immunoprecipitation sequencing, and adeno-associated virus experiments in vivo were performed to explore the downstream molecules of SP1. To examine the therapeutic effect of SP1 on HCM, an SP1 overexpression vector was constructed and injected into the mutant allele of Myh6 R404Q\/+ (\n              <jats:italic toggle=\"yes\">Myh6<\/jats:italic>\n              c. 1211C&gt;T) HCM mice. The human induced pluripotent stem cell\u2013derived cardiomyocytes (hiPSC-CMs) from a patient with HCM were used to detect the potential therapeutic effects of SP1 in human HCM.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              The cardiac-specific conditional knockout of\n              <jats:italic toggle=\"yes\">Sp1<\/jats:italic>\n              mice developed a typical HCM phenotype, displaying overt myocardial hypertrophy, interstitial fibrosis, and disordered myofilament. In addition,\n              <jats:italic toggle=\"yes\">Sp1<\/jats:italic>\n              knockdown dramatically increased the cell area of hiPSC-CMs and caused intracellular myofibrillar disorganization, which was similar to the hypertrophic cardiomyocytes of HCM. Mechanistically,\n              <jats:italic toggle=\"yes\">Tuft1<\/jats:italic>\n              was identified as the key target gene of SP1. The hypertrophic phenotypes induced by\n              <jats:italic toggle=\"yes\">Sp1<\/jats:italic>\n              knockdown in both hiPSC-CMs and mice could be rescued by TUFT1 (tuftelin 1) overexpression. Furthermore, SP1 overexpression suppressed the development of HCM in the mutant allele of Myh6 R404Q\/+ mice and also reversed the hypertrophic phenotype of HCM hiPSC-CMs.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our study demonstrates that SP1 deficiency leads to HCM. SP1 overexpression exhibits significant therapeutic effects on both HCM mice and HCM hiPSC-CMs, suggesting that SP1 could be a potential intervention target for HCM.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.123.323272","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T05:00:29Z","timestamp":1704862829000},"page":"290-306","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Deficiency of Transcription Factor Sp1 Contributes to Hypertrophic Cardiomyopathy"],"prefix":"10.1161","volume":"134","author":[{"given":"Fulei","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixing","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine (J.X., L.Q.), Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuemei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Leng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojian","family":"Fang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Jinzhou Medical University, China (Yuanyuan Liu, Y. Wang, Yan Wang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Jinzhou Medical University, China (Yuanyuan Liu, Y. Wang, Yan Wang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahan","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingbin","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine (J.X., L.Q.), Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Duan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Jinzhou Medical University, China (Yuanyuan Liu, Y. Wang, Yan Wang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Pathology and Pathophysiology (L.L., J.Y., Y.-H.C.), Tongji University School of Medicine, Shanghai, China."},{"name":"Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai, China (L.L., J.Y., D.L., Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1964-7061","authenticated-orcid":true,"given":"Jian","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Pathology and Pathophysiology (L.L., J.Y., Y.-H.C.), Tongji University School of Medicine, Shanghai, China."},{"name":"Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai, China (L.L., J.Y., D.L., Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1112-8996","authenticated-orcid":true,"given":"Dandan","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Shanghai Arrhythmias Research Center (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., Yuanyuan Liu, Y. Wang, H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Department of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China."},{"name":"Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai, China (L.L., J.Y., D.L., Y.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1000-1835","authenticated-orcid":true,"given":"Yi-Han","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. 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