{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:05:00Z","timestamp":1783595100853,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T00:00:00Z","timestamp":1518048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Talent Program of Tianjin Medical University","award":["11601501\/2016KJ0317"],"award-info":[{"award-number":["11601501\/2016KJ0317"]}]},{"name":"Thousand Talents Plan of Tianjin","award":["11601501\/2016DW0202"],"award-info":[{"award-number":["11601501\/2016DW0202"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2018,4]]},"abstract":"Summary<\/jats:title>Background<\/jats:title>Myocardial infarction (MI<\/jats:styled-content>) remains the most common cause of heart failure (HF<\/jats:styled-content>) worldwide. For almost 50\u00a0years, HF<\/jats:styled-content> has been recognized as a determinant of adverse prognosis after MI<\/jats:styled-content>, but efforts to promote myocardial repair have failed to be translated into clinical therapies.<\/jats:p><\/jats:sec>Aims<\/jats:title>In this study, we investigated the effects of BRD<\/jats:styled-content>4 on cardiac function and the underlying mechanism.<\/jats:p><\/jats:sec>Material and Methods<\/jats:title>The in vivo rat model of AMI and in vitro neonatal cardiomyocytes were established and cultured respectively, the BRD4 and NPPA\/NPPB expression levels were detected by qPCR and Western blot, and interaction of BRD4 with acetylation RelA or NPPA\/B promoters were examined by co\u2010immunoprecipitation and chromatin immunoprecipitation assays, respectively.<\/jats:p><\/jats:sec>Results<\/jats:title>We found that BRD<\/jats:styled-content>4 protein expression was significantly increased in cardiomyocytes of MI<\/jats:styled-content> rat model and cardiomyocytes under hypoxia, accompanied by the expression of natriuretic peptide A (NPPA<\/jats:styled-content>) and natriuretic peptide B (NPPB<\/jats:styled-content>). Functionally, knockdown of BRD<\/jats:styled-content>4 greatly downregulated the NPPA<\/jats:styled-content> and NPPB<\/jats:styled-content> in vivo and in vitro, improved the hemodynamic and biometric parameters in rat with heart failure, as well as decreased the apoptosis occurrence. In vitro studies further demonstrated that BRD<\/jats:styled-content>4 bound with acetylated RelA to enhance the activation of NF<\/jats:styled-content>\u2010\u03bab signaling, which resulted in activation of NPPA<\/jats:styled-content> and NPPB<\/jats:styled-content> transcriptions.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Taken together, our findings suggest that inhibition of BRD<\/jats:styled-content>4 attenuated cardiomyocyte apoptosis via NF<\/jats:styled-content>\u2010\u03baB pathway in myocardial infarction, and this study sheds light on developing new strategies to overcome myocardial damage.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12320","type":"journal-article","created":{"date-parts":[[2018,1,20]],"date-time":"2018-01-20T06:52:41Z","timestamp":1516431161000},"source":"Crossref","is-referenced-by-count":36,"title":["Inhibition of BRD<\/scp>4 attenuates cardiomyocyte apoptosis via NF<\/scp>\u2010\u03baB pathway in a rat model of myocardial infarction"],"prefix":"10.1111","volume":"36","author":[{"given":"Yiping","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery the Affiliated Zhongshan Hospital of Fudan University Xuhui Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology School of Basic Medical Science Tianjin Medical University Heping Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luping","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology School of Basic Medical Science Tianjin Medical University Heping Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology the Affiliated Hospital of Binzhou Medical University Binzhou Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0677-8097","authenticated-orcid":false,"given":"Zhiqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology School of Basic Medical Science Tianjin Medical University Heping Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2296-8-11"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000142856.56565.56"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020265"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-016-9381-z"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2015.2789"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.05.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-015-3319-1"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.07.017"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.86"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2015.09.074"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0166845"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.07.015"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047306"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.179"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00472.2006"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.138"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152767"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/10245332.2016.1258152"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.18.7966-7975.2005"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.20.2093"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0416-361"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aah5084"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.013"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705053104"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.902196"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2015.04.025"}],"container-title":["Cardiovascular 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