{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T23:26:40Z","timestamp":1782170800946,"version":"3.54.5"},"reference-count":33,"publisher":"Georg Thieme Verlag KG","issue":"10","funder":[{"name":"Diagnosis and treatment of cardiovascular diseases based on glycolysis","award":["JCYJ20170412150405310"],"award-info":[{"award-number":["JCYJ20170412150405310"]}]},{"name":"3D printing and rapid prototyping\n                        technology in the treatment of Complex abdominal aortic\n                        aneurysm","award":["SZFZ2018071"],"award-info":[{"award-number":["SZFZ2018071"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Objective Diabetic cardiomyopathy (DCM) constitutes a primary cause of\n                    mortality in diabetic patients. Histone deacetylase (HDAC) inhibition can\n                    alleviate diabetes-associated myocardial injury. This study investigated the\n                    mechanism of HDAC1 on myocardial fibrosis (MF) in DCM.<\/jats:p><jats:p>\n          Methods A murine model of DCM was established by a high-fat diet and\n                    streptozotocin injection. The bodyweight, blood glucose, serum insulin, and\n                    cardiac function of mice were analyzed. Lentivirus-packaged sh-HDAC1 was\n                    injected into DCM mice and high glucose (HG)-induced cardiac fibroblasts (CFs).\n                    The pathological structure of the myocardium and the level of myocardial\n                    fibrosis were observed by histological staining. HDAC1 expression in mouse\n                    myocardial tissues and CFs was determined. Collagen I, collagen III,\n                    alpha-smooth muscle actin (\u03b1-SMA), and vimentin levels in CFs were\n                    detected, and CF proliferation was tested. HDAC activity and histone acetylation\n                    levels in tissues and cells were measured. Bone morphogenetic protein-7 (BMP-7)\n                    expression in myocardial tissues and CFs was determined. Functional rescue\n                    experiments were conducted to confirm the effects of histone acetylation and\n                    BMP-7 on myocardial fibrosis.<\/jats:p><jats:p>\n          Results DCM mice showed decreased bodyweight, elevated blood glucose and\n                    serum insulin, and cardiac dysfunction. Elevated HDAC1 and reduced BMP-7\n                    expressions were detected in DCM mice and HG-induced CFs. HDAC1 repressed BMP-7\n                    transcription through deacetylation. HDAC1 silencing alleviated MF, reduced CF\n                    proliferation and decreased collagen I, -III, \u03b1-SMA, and vimentin\n                    levels. However, reducing histone acetylation level or BMP-7 downregulation\n                    reversed the effects of HDAC1 silencing on CF fibrosis.<\/jats:p><jats:p>\n          Conclusion HDAC1 repressed BMP-7 transcription by enhancing histone\n                    deacetylation, thereby promoting MF and aggravating DCM.<\/jats:p>","DOI":"10.1055\/a-1780-8768","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T23:12:28Z","timestamp":1656371548000},"page":"660-670","source":"Crossref","is-referenced-by-count":10,"title":["HDAC1 Promotes Myocardial Fibrosis in Diabetic Cardiomyopathy by\n                    Inhibiting BMP-7 Transcription Through Histone Deacetylation"],"prefix":"10.1055","volume":"130","author":[{"given":"Chun","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Peking University Shenzhen\n                    Hospital, Shenzhen City 518036, Guangdong Province, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Peking University Shenzhen\n                    Hospital, Shenzhen City 518036, Guangdong Province, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Peking University Shenzhen\n                    Hospital, Shenzhen City 518036, Guangdong Province, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Peking University Shenzhen\n                    Hospital, Shenzhen City 518036, Guangdong Province, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Peking University Shenzhen\n                    Hospital, Shenzhen City 518036, Guangdong Province, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.7257\/1053-816X.2016.36.1.27","article-title":"Diabetes mellitus review","volume":"36","author":"M Blair","year":"2016","journal-title":"Urol Nurs"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41581-020-0278-5","article-title":"Genetics of diabetes mellitus and diabetes complications","volume":"16","author":"J B Cole","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"598012","DOI":"10.3389\/fendo.2020.598012","article-title":"Epigenetic regulation associated with sirtuin 1 in complications of diabetes\n                    mellitus","volume":"11","author":"A J Wang","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00125-017-4390-4","article-title":"Diabetic cardiomyopathy: A hyperglycaemia- and insulin-resistance-induced heart\n                    disease","volume":"61","author":"G Jia","year":"2018","journal-title":"Diabetologia"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1161\/CIRCRESAHA.118.314665","article-title":"Diabetic cardiomyopathy","volume":"124","author":"W H Dillmann","year":"2019","journal-title":"Circ Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.yjmcc.2016.02.011","article-title":"Epigenetic regulation of cardiac fibrosis","volume":"92","author":"M S Stratton","year":"2016","journal-title":"J Mol Cell Cardiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.diabres.2011.05.033","article-title":"Epigenetics and diabetic cardiomyopathy","volume":"94","author":"G B Singh","year":"2011","journal-title":"Diabetes Res Clin Pract"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"20170067","DOI":"10.1098\/rstb.2017.0067","article-title":"Epigenetics: The first 25 centuries","volume":"373","author":"A Ganesan","year":"2018","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1042\/CS20170064","article-title":"Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via\n                    epigenetic regulation of DUSP5-ERK1\/2 pathway","volume":"131","author":"Z Xu","year":"2017","journal-title":"Clin Sci (Lond)"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.yjmcc.2019.04.003","article-title":"Histone deacetylases in cardiovascular and metabolic diseases","volume":"130","author":"R A Bagchi","year":"2019","journal-title":"J Mol Cell Cardiol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s12933-015-0262-8","article-title":"Histone deacetylase (HDAC) inhibition improves myocardial function and prevents\n                    cardiac remodeling in diabetic mice","volume":"14","author":"Y Chen","year":"2015","journal-title":"Cardiovasc Diabetol"},{"key":"ref12","first-page":"5938740","article-title":"HDAC inhibition modulates cardiac PPARs and fatty acid metabolism in diabetic\n                    cardiomyopathy","volume":"2016","author":"T I Lee","year":"2016","journal-title":"PPAR Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"8008","DOI":"10.1096\/fj.201900127R","article-title":"STAT3 phosphorylation mediates high glucose-impaired cell autophagy in an\n                    HDAC1-dependent and -independent manner in Schwann cells of diabetic peripheral\n                    neuropathy","volume":"33","author":"W Du","year":"2019","journal-title":"FASEB J"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"108570","DOI":"10.1016\/j.biopha.2019.01.031","article-title":"Puerarin alleviates streptozotocin (STZ)-induced osteoporosis in rats through\n                    suppressing inflammation and apoptosis via HDAC1\/HDAC3 signaling","volume":"115","author":"C J Guo","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.yjmcc.2013.12.013","article-title":"Class I HDACs regulate angiotensin II-dependent cardiac fibrosis via fibroblasts\n                    and circulating fibrocytes","volume":"67","author":"S M Williams","year":"2014","journal-title":"J Mol Cell Cardiol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1755-1536-7-10","article-title":"HDAC class I inhibitor, Mocetinostat, reverses cardiac fibrosis in heart failure\n                    and diminishes CD90+cardiac myofibroblast activation","volume":"7","author":"H F Nural-Guvener","year":"2014","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1016\/j.yexcr.2010.07.004","article-title":"High levels of glucose induce apoptosis in cardiomyocyte via epigenetic\n                    regulation of the insulin-like growth factor receptor","volume":"316","author":"X Y Yu","year":"2010","journal-title":"Exp Cell Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3390\/cells9020280","article-title":"The role of bone morphogenetic protein 7 (BMP-7) in inflammation in heart\n                    diseases","volume":"9","author":"C Aluganti Narasimhulu","year":"2020","journal-title":"Cells"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1620\/tjem.244.1","article-title":"Exogenous BMP-7 facilitates the recovery of cardiac function after acute\n                    myocardial infarction through counteracting TGF-beta1 signaling pathway","volume":"244","author":"Y Jin","year":"2018","journal-title":"Tohoku J Exp Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"H762","DOI":"10.1152\/ajpheart.00367.2014","article-title":"BMP-7 attenuates adverse cardiac remodeling mediated through M2 macrophages in\n                    prediabetic cardiomyopathy","volume":"307","author":"P Urbina","year":"2014","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and\n                    the 2(-Delta Delta C(T)) Method","volume":"25","author":"K J Livak","year":"2001","journal-title":"Methods"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"5249","DOI":"10.1111\/jcmm.15178","article-title":"Overexpression of peptidase inhibitor 16 attenuates angiotensin II-induced\n                    cardiac fibrosis via regulating HDAC1 of cardiac fibroblasts","volume":"24","author":"M Deng","year":"2020","journal-title":"J Cell Mol Med"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.3390\/ijms22041600","article-title":"Nuclear receptor nur77 controls cardiac fibrosis through distinct actions on\n                    fibroblasts and cardiomyocytes","volume":"22","author":"L Medzikovic","year":"2021","journal-title":"Int J Mol Sci"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"909","DOI":"10.4093\/dmj.2020.0168","article-title":"Sulforaphane ameliorates diabetes-induced renal fibrosis through epigenetic\n                    up-regulation of BMP-7","volume":"45","author":"L Kong","year":"2021","journal-title":"Diabetes Metab J"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e9288","DOI":"10.1590\/1414-431x20209288","article-title":"LncRNA ZEB1-AS1 inhibits high glucose-induced EMT and fibrogenesis by regulating\n                    the miR-216a-5p\/BMP7 axis in diabetic nephropathy","volume":"53","author":"Q Meng","year":"2020","journal-title":"Braz J Med Biol Res"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12933-017-0506-x","article-title":"Diagnostic approaches for diabetic cardiomyopathy","volume":"16","author":"A Lorenzo-Almoros","year":"2017","journal-title":"Cardiovasc Diabetol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1161\/CIRCRESAHA.109.209338","article-title":"Protein acetylation in the cardiorenal axis: The promise of histone deacetylase\n                    inhibitors","volume":"106","author":"E W Bush","year":"2010","journal-title":"Circ Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.bbadis.2016.11.006","article-title":"The role of alpha-smooth muscle actin in fibroblast-mediated matrix contraction\n                    and remodeling","volume":"1863","author":"A V Shinde","year":"2017","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10741-018-9720-1","article-title":"Biomarkers for the identification of cardiac fibroblast and myofibroblast\n                    cells","volume":"24","author":"E Tarbit","year":"2019","journal-title":"Heart Fail Rev"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1002\/ehf2.12360","article-title":"Circulating markers of collagen types I, III, and IV in patients with dilated\n                    cardiomyopathy: Relationships with myocardial collagen expression","volume":"5","author":"K Nagao","year":"2018","journal-title":"ESC Heart Fail"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2131\/jts.44.425","article-title":"Ellagic acid inhibits proliferation and migration of cardiac fibroblasts by\n                    down-regulating expression of HDAC1","volume":"44","author":"C Lin","year":"2019","journal-title":"J Toxicol Sci"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1111\/jcmm.14162","article-title":"Acetyltransferase p300 inhibitor reverses hypertension-induced cardiac\n                    fibrosis","volume":"23","author":"R Rai","year":"2019","journal-title":"J Cell Mol Med"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.12659\/MSM.897560","article-title":"Bone morphogenetic protein-7 antagonizes myocardial fibrosis induced by atrial\n                    fibrillation by restraining transforming growth factor-beta\n                    (TGF-beta)\/Smads signaling","volume":"22","author":"X Chen","year":"2016","journal-title":"Med Sci Monit"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1780-8768.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:15:00Z","timestamp":1666138500000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1780-8768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,27]]},"references-count":33,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10,18]]},"published-print":{"date-parts":[[2022,10]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1780-8768","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,27]]}}}