{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:05:25Z","timestamp":1790301925299,"version":"4.1.0"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,9,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Apoptosis plays a pivotal role in cardiac rupture after myocardial infarction (MI), and p53 is a key molecule in apoptosis during cardiac rupture. Hif\u20101\u03b1 (hypoxia\u2010inducible factor\u20101\u03b1), upregulated under hypoxia, is a known p53 inducer. However, the role of Hif\u20101\u03b1 in the regulatory mechanisms underlying p53 upregulation, apoptosis, and cardiac rupture after MI is unclear.<\/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\">We induced MI in mice by ligating the left anterior descending artery. Hif\u20101\u03b1 and p53 expressions were upregulated in the border zone at day 5 after MI, accompanied by apoptosis. In rat neonatal cardiomyocytes, treatment with cobalt chloride (500\u00a0\u03bcmol\/L), which mimics severe hypoxia by inhibiting PHD (prolyl hydroxylase domain\u2010containing protein), increased Hif\u20101\u03b1 and p53, accompanied by myocyte death with caspase\u20103 cleavage. Silencing Hif\u20101\u03b1 or p53 inhibited caspase\u20103 cleavage, and completely prevented myocyte death under PHD inhibition. In cardiac\u2010specific Hif\u20101\u03b1 hetero\u2010knockout mice, expression of p53 and cleavage of caspase\u20103 and poly (ADP\u2010ribose) polymerase were reduced, and apoptosis was suppressed on day 5. Furthermore, the cleavage of caspase\u20108 and IL\u20101\u03b2 (interleukin\u20101\u03b2) was also suppressed in hetero knockout mice, accompanied by reduced macrophage infiltration and matrix metalloproteinase\/tissue inhibitor of metalloproteinase activation. Although there was no intergroup difference in infarct size, the cardiac rupture and survival rates were significantly improved in the hetero knockout mice until day 10 after MI.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Hif\u20101\u03b1 plays a pivotal role in apoptosis, inflammation, and cardiac rupture after MI, in which p53 is a critical mediator, and may be a prospective therapeutic target for preventing cardiac rupture.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.020895","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T09:08:17Z","timestamp":1630573697000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":44,"title":["Excessive Hypoxia\u2010Inducible Factor\u20101\u03b1 Expression Induces Cardiac Rupture via p53\u2010Dependent Apoptosis After Myocardial Infarction"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-8171","authenticated-orcid":false,"given":"Masataka","family":"Ikeda","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Ide","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7360-672X","authenticated-orcid":false,"given":"Tomonori","family":"Tadokoro","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko Deguchi","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Okabe","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihito","family":"Ishikita","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Furusawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosei","family":"Ishimaru","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9774-4513","authenticated-orcid":false,"given":"Shouji","family":"Matsushima","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsutsui","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Faculty of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Division of Cardiovascular Medicine Research Institute of Angiocardiology Faculty of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.776690"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/CRD.0b013e3181bf4ab4"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/13459"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8768"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00207.2003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000147233.10318.23"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.02.001"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-020-07123-5"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20150517"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/32925"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.021"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.04.009"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.07.028"},{"key":"e_1_3_2_15_2","first-page":"4010","article-title":"Hypoxia\u2010inducible factor\u20101\u03b1 is a positive factor in solid tumor growth","volume":"60","author":"Ryan HE","year":"2000","unstructured":"Ryan HE, Poloni M, McNulty W, Elson D, Gassmann M, Arbeit JM, Johnson RS. Hypoxia\u2010inducible factor\u20101\u03b1 is a positive factor in solid tumor growth. Cancer Res. 2000;60:4010\u20134015.","journal-title":"Cancer Res"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119509"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00044.2016"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119687"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-19-1039"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2012.06.002"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.132747"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep15881"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00090.2016"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.10.014"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.05.020"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004714200"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.09.022"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.305109"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvm035"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.08.045"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3769"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.186809"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.01.007"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20020238"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/0962-8924(93)90128-N"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.09.008"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.922427"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs014"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-117812"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011693"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs145"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06639-7"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2019.04.039"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.04.011"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31356-8"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa409"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccas.2020.05.089"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccas.2020.05.049"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccas.2020.06.037"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.12.072"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.04.020"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.712"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(03)00883-X"},{"key":"e_1_3_2_54_2","first-page":"921","article-title":"Mechanisms for the early mortality reduction produced by beta\u2010blockade started early in acute myocardial infarction: ISIS\u20101. ISIS\u20101 (First International Study of Infarct Survival) Collaborative Group","volume":"1","year":"1988","unstructured":"Mechanisms for the early mortality reduction produced by beta\u2010blockade started early in acute myocardial infarction: ISIS\u20101. ISIS\u20101 (First International Study of Infarct Survival) Collaborative Group. Lancet. 1988;1:921\u2013923.","journal-title":"Lancet"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.01.035"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-018-9809-x"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06091"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv484"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.020895","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:43:19Z","timestamp":1715600599000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.020895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,7]]},"references-count":57,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2021,9,7]]}},"alternative-id":["10.1161\/JAHA.121.020895"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.020895","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,7]]},"assertion":[{"value":"2021-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e020895"}}