{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:56:37Z","timestamp":1791615397208,"version":"4.3.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T00:00:00Z","timestamp":1609545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stafford Fox Medical Research Foundation"},{"DOI":"10.13039\/501100004752","name":"Victorian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004752","id-type":"DOI","asserted-by":"publisher"}]},{"name":"5 Point Foundation Christine Martin Fellow"},{"name":"St Vincent\u2019s Institute"},{"name":"Vice Chancellors Fellow at RMIT University"},{"name":"Agencia Nacional de Ciencia y Desarrollo"},{"DOI":"10.13039\/501100002850","name":"FONDECYT","doi-asserted-by":"publisher","award":["11181000"],"award-info":[{"award-number":["11181000"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018735","name":"FONDAP","doi-asserted-by":"publisher","award":["15130011"],"award-info":[{"award-number":["15130011"]}],"id":[{"id":"10.13039\/501100018735","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council Core funding to the MRC LMCB","award":["MC_U12266B"],"award-info":[{"award-number":["MC_U12266B"]}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["CS\/14\/3\/31002"],"award-info":[{"award-number":["CS\/14\/3\/31002"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre"},{"name":"Duke-National University Singapore Medical School"},{"name":"Singapore Ministry of Health\u2019s National Medical Research"},{"name":"Clinician Scientist-Senior Investigator scheme","award":["NMRC\/CSA-SI\/0011\/2017"],"award-info":[{"award-number":["NMRC\/CSA-SI\/0011\/2017"]}]},{"name":"Collaborative Centre Grant scheme","award":["NMRC\/CGAug16C006"],"award-info":[{"award-number":["NMRC\/CGAug16C006"]}]},{"name":"Singapore Ministry of Education Academic Research Fund Tier 2","award":["MOE2016-T2-2-021"],"award-info":[{"award-number":["MOE2016-T2-2-021"]}]},{"name":"COST Action EU-CARDIOPROTECTION CA16225 supported by COST"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Genetic and pharmacological inhibition of mitochondrial fission induced by acute myocardial ischaemia\/reperfusion injury (IRI) has been shown to reduce myocardial infarct size. The clinically used anti-hypertensive and heart failure medication, hydralazine, is known to have anti-oxidant and anti-apoptotic effects. Here, we investigated whether hydralazine confers acute cardioprotection by inhibiting Drp1-mediated mitochondrial fission.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Pre-treatment with hydralazine was shown to inhibit both mitochondrial fission and mitochondrial membrane depolarisation induced by oxidative stress in HeLa cells. In mouse embryonic fibroblasts (MEFs), pre-treatment with hydralazine attenuated mitochondrial fission and cell death induced by oxidative stress, but this effect was absent in MEFs deficient in the mitochondrial fission protein, Drp1. Molecular docking and surface plasmon resonance studies demonstrated binding of hydralazine to the GTPase domain of the mitochondrial fission protein, Drp1 (KD 8.6\u00b11.0\u00a0\u00b5M), and inhibition of Drp1 GTPase activity in a dose-dependent manner. In isolated adult murine cardiomyocytes subjected to simulated IRI, hydralazine inhibited mitochondrial fission, preserved mitochondrial fusion events, and reduced cardiomyocyte death (hydralazine 24.7\u00b12.5% vs. control 34.1\u00b11.5%, P=0.0012). In ex vivo perfused murine hearts subjected to acute IRI, pre-treatment with hydralazine reduced myocardial infarct size (as % left ventricle: hydralazine 29.6\u00b16.5% vs. vehicle control 54.1\u00b14.9%, P=0.0083), and in the murine heart subjected to in vivo IRI, the administration of hydralazine at reperfusion, decreased myocardial infarct size (as % area-at-risk: hydralazine 28.9\u00b13.0% vs. vehicle control 58.2\u00b13.8%, P&amp;lt;0.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We show that, in addition to its antioxidant and anti-apoptotic effects, hydralazine, confers acute cardioprotection by inhibiting IRI-induced mitochondrial fission, raising the possibility of repurposing hydralazine as a novel cardioprotective therapy for improving post-infarction outcomes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaa343","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T12:31:11Z","timestamp":1607603471000},"page":"282-294","source":"Crossref","is-referenced-by-count":61,"title":["Hydralazine protects the heart against acute ischaemia\/reperfusion injury by inhibiting Drp1-mediated mitochondrial fission"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3401-9335","authenticated-orcid":false,"given":"Siavash Beikoghli","family":"Kalkhoran","sequence":"first","affiliation":[{"name":"The Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College, 67 Chenies Mews, WC1E 6HX London, UK"},{"name":"Cardiovascular and Metabolic Disorder Programme, Duke-NUS Medical School, 8 College Road, 169857, Singapore"},{"name":"National Heart Research Institute Singapore, National Heart Centre, 5 Hospital Drive, 169609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0149-145X","authenticated-orcid":false,"given":"Janos","family":"Kriston-Vizi","sequence":"additional","affiliation":[{"name":"MRC Laboratory for Molecular Cell Biology, University College, Gower St, Kings Cross, WC1E 6BT London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sauri","family":"Hernandez-Resendiz","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorder Programme, Duke-NUS Medical School, 8 College Road, 169857, Singapore"},{"name":"National Heart Research Institute Singapore, National Heart Centre, 5 Hospital Drive, 169609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2283-6434","authenticated-orcid":false,"given":"Gustavo E","family":"Crespo-Avilan","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorder Programme, Duke-NUS Medical School, 8 College Road, 169857, Singapore"},{"name":"National Heart Research Institute Singapore, National Heart Centre, 5 Hospital Drive, 169609, Singapore"},{"name":"Department of Biochemistry, Medical Faculty, Justus Liebig-University, Ludwigstra\u00dfe 23, 35390 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6113-2101","authenticated-orcid":false,"given":"Ayeshah A","family":"Rosdah","sequence":"additional","affiliation":[{"name":"O\u2019Brien Institute Department, St Vincent\u2019s Institute of Medical Research, 9 Princes Street Fitzroy Victoria, 3065, Australia"},{"name":"Faculty of Medicine, Universitas Sriwijaya, Palembang, Bukit Lama, Kec. Ilir Bar. I, Kota Palembang, 30139 Sumatera Selatan, Indonesia"},{"name":"Department of Surgery and Medicine, University of Melbourne, Medical Building, Cnr Grattan Street & Royal Parade, 3010 Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9259-8657","authenticated-orcid":false,"given":"Jarmon G","family":"Lees","sequence":"additional","affiliation":[{"name":"O\u2019Brien Institute Department, St Vincent\u2019s Institute of Medical Research, 9 Princes Street Fitzroy Victoria, 3065, Australia"},{"name":"Department of Surgery and Medicine, University of Melbourne, Medical Building, Cnr Grattan Street & Royal Parade, 3010 Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana Rodrigues Simoes Da","family":"Costa","sequence":"additional","affiliation":[{"name":"MRC Laboratory for Molecular Cell Biology, University College, Gower St, Kings Cross, WC1E 6BT London, 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