{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:02:11Z","timestamp":1792695731680,"version":"4.5.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,7,6]]},"abstract":"\n Background<\/jats:title>\n \n Mitochondria\u2010mediated cell death plays a critical role in myocardial ischemia\u2010reperfusion (\n IR<\/jats:styled-content>\n ) injury. We hypothesized that nanoparticle\u2010mediated drug delivery of mitochondrial division inhibitor 1 (Mdivi1) protects hearts from\n IR<\/jats:styled-content>\n injury through inhibition of mitochondria outer membrane permeabilization (\n MOMP<\/jats:styled-content>\n ), which causes mitochondrial\u2010mediated cell death.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We formulated poly (lactic\u2010co\u2010glycolic acid) nanoparticles containing Mdivi1 (Mdivi1\u2010\n NP<\/jats:styled-content>\n ). We recently demonstrated that these nanoparticles could be successfully delivered to the cytosol and mitochondria of cardiomyocytes under H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n \u2010induced oxidative stress that mimicked\n IR<\/jats:styled-content>\n injury. Pretreatment with Mdivi1\u2010\n NP<\/jats:styled-content>\n ameliorated H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n \u2010induced cell death in rat neonatal cardiomyocytes more potently than Mdivi1 alone, as indicated by a lower estimated half\u2010maximal effective concentration and greater maximal effect on cell survival. Mdivi1\u2010\n NP<\/jats:styled-content>\n treatment of Langendorff\u2010perfused mouse hearts through the coronary arteries at the time of reperfusion reduced infarct size after\n IR<\/jats:styled-content>\n injury more effectively than Mdivi1 alone. Mdivi1\u2010\n NP<\/jats:styled-content>\n treatment also inhibited Drp1\u2010mediated Bax translocation to the mitochondria and subsequent cytochrome\n c<\/jats:italic>\n leakage into the cytosol, namely,\n MOMP<\/jats:styled-content>\n , in mouse\n IR<\/jats:styled-content>\n hearts.\n MOMP<\/jats:styled-content>\n inhibition was also observed in cyclophilin D knockout (CypD\u2010\n KO<\/jats:styled-content>\n ) mice, which lack the mitochondrial permeability transition pore (\n MPTP<\/jats:styled-content>\n ) opening. Intravenous Mdivi1\u2010\n NP<\/jats:styled-content>\n treatment in\u00a0vivo at the time of reperfusion reduced\n IR<\/jats:styled-content>\n injury in wild\u2010type and CypD\u2010\n KO<\/jats:styled-content>\n mice, but not Bax\u2010\n KO<\/jats:styled-content>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Mdivi1\u2010\n NP<\/jats:styled-content>\n treatment reduced\n IR<\/jats:styled-content>\n injury through inhibition of\n MOMP<\/jats:styled-content>\n , even in the absence of a CypD\/\n MPTP<\/jats:styled-content>\n opening. Thus, nanoparticle\u2010mediated drug delivery of Mdivi1 may be a novel treatment strategy for\n IR<\/jats:styled-content>\n injury.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.116.003872","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T10:10:42Z","timestamp":1505729442000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":99,"title":["Nanoparticle\u2010Mediated Delivery of Mitochondrial Division Inhibitor 1 to the Myocardium Protects the Heart From Ischemia\u2010Reperfusion Injury Through Inhibition of Mitochondria Outer Membrane Permeabilization: A New Therapeutic Modality for Acute Myocardial Infarction"],"prefix":"10.1161","volume":"5","author":[{"given":"Ayako","family":"Ishikita","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Matoba","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gentaro","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010ichiro","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"},{"name":"Department of Cardiovascular Research, Development, and Translational Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, 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