{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:24:01Z","timestamp":1783661041947,"version":"3.55.0"},"reference-count":68,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,5,16]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. PI16 (peptidase inhibitor 16), as a secreted protein, is highly expressed in heart diseases such as heart failure. However, the functional role of PI16 in MI is unknown. This study aimed to investigate the role of PI16 after MI and its underlying mechanisms.<\/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\">PI16 levels after MI were measured by enzyme\u2010linked immunosorbent assay and immunofluorescence staining, which showed that PI16 was upregulated in the plasma of patients with acute MI and in the infarct zone of murine hearts. PI16 gain\u2010 and loss\u2010of\u2010function experiments were used to investigate the potential role of PI16 after MI. In vitro, PI16 overexpression inhibited oxygen\u2013glucose deprivation\u2013induced apoptosis in neonatal rat cardiomyocytes, whereas knockdown of PI16 exacerbated neonatal rat cardiomyocyte apoptosis. In vivo, left anterior descending coronary artery ligation was performed on PI16 transgenic mice, PI16 knockout mice, and their littermates. PI16 transgenic mice showed decreased cardiomyocyte apoptosis at 24\u2009hours after MI and improved left ventricular remodeling at 28\u2009days after MI. Conversely, PI16 knockout mice showed aggravated infract size and remodeling. Mechanistically, PI16 downregulated Wnt3a (wingless\u2010type MMTV integration site family, member 3a)\/\u03b2\u2010catenin pathways, and the antiapoptotic role of PI16 was reversed by recombinant Wnt3a in oxygen\u2013glucose deprivation\u2013induced neonatal rat cardiomyocytes. PI16 also inhibited HDAC1 (class I histone deacetylase) expression, and overexpression HDAC1 abolished the inhibition of apoptosis and Wnt signaling of PI16.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">In summary, PI16 protects against cardiomyocyte apoptosis and left ventricular remodeling after MI through the HDAC1\u2010Wnt3a\u2010\u03b2\u2010catenin axis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.028866","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T12:54:23Z","timestamp":1683636863000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Peptidase Inhibitor 16 Attenuates Left Ventricular Injury and Remodeling After Myocardial Infarction by Inhibiting the HDAC1\u2010Wnt3a\u2010\u03b2\u2010Catenin Signaling Axis"],"prefix":"10.1161","volume":"12","author":[{"given":"Luyang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anning","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"},{"name":"School of Medicine Southeast University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-1772","authenticated-orcid":false,"given":"Zhenyang","family":"Su","sequence":"additional","affiliation":[{"name":"School of Medicine Southeast University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1796-5637","authenticated-orcid":false,"given":"Huanyu","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0833-0445","authenticated-orcid":false,"given":"Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqing","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu China"},{"name":"Cardiovascular Research Center The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.09.019"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.942268"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac223"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0045(19990201)38:2<118::AID-PROS5>3.0.CO;2-G"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040290"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.696468"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201948094"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-324868"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.08.010"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.117.013896"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-018-0705-y"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808393105"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075010"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00891.2006"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002416"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15178"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13619-015-0017-8"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303577"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3331"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201847552"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.914033"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI152418"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.055888"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046789"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00455-6"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2012.04.002"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep39553"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-014-0424-y"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz207"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0022-z"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2016.05.007"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.322"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.612648"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000093186.22847.4C"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.006510"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002457"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.976969"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-018-9759-z"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603916200"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200128"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.250282"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2020.155237"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1177\/02676591221076788"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610024104"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.16966\/2472-6990.111"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.03.030"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastrohep.2019.02.006"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.232280"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004708107"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.950960"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11626-022-00646-1"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14327"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2015.06.028"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-021-00741-y"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-88928-8"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3675"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-17-0022"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2034583"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-15743-0"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.07.004"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00390.2014"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001260"},{"key":"e_1_3_2_64_2","first-page":"744","article-title":"HDAC I inhibitor regulates RUNX2 transactivation through canonical and non\u2010canonical Wnt signaling in aortic valvular interstitial cells","volume":"11","author":"Li SJ","year":"2019","unstructured":"Li SJ, Kao YH, Chung CC, Cheng WL, Chen YJ. HDAC I inhibitor regulates RUNX2 transactivation through canonical and non\u2010canonical Wnt signaling in aortic valvular interstitial cells. Am J Transl Res. 2019;11:744\u2013754.","journal-title":"Am J Transl Res"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-022-03224-z"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf616"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-13-20"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/0470862637.ch14"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19173-2"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.122.028866","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T12:34:52Z","timestamp":1715603692000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.122.028866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,16]]},"references-count":68,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,5,16]]}},"alternative-id":["10.1161\/JAHA.122.028866"],"URL":"https:\/\/doi.org\/10.1161\/jaha.122.028866","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,16]]},"assertion":[{"value":"2022-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e028866"}}