{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:53:33Z","timestamp":1784375613225,"version":"3.55.0"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2013,11,18]]},"abstract":"\n Background<\/jats:title>\n \n Recent evidence has depicted a role of macrophage migration inhibitory factor (\n MIF<\/jats:styled-content>\n ) in cardiac homeostasis under pathological conditions. This study was designed to evaluate the role of\n MIF<\/jats:styled-content>\n in doxorubicin\u2010induced cardiomyopathy and the underlying mechanism involved with a focus on autophagy.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Wild\u2010type (WT) and\n MIF<\/jats:styled-content>\n knockout (\n MIF<\/jats:styled-content>\n \u2212\/\u2212<\/jats:sup>\n ) mice were given saline or doxorubicin (20\u00a0mg\/kg cumulative, i.p.). A cohort of\n WT<\/jats:styled-content>\n and\n MIF<\/jats:styled-content>\n \u2212\/\u2212<\/jats:sup>\n mice was given rapamycin (6\u00a0mg\/kg, i.p.) with or without bafilomycin A1 (BafA1, 3\u00a0\u03bcmol\/kg per day, i.p.) for 1\u00a0week prior to doxorubicin challenge. To consolidate a role for\n MIF<\/jats:styled-content>\n in the maintenance of cardiac homeostasis following doxorubicin challenge, recombinant mouse\n MIF<\/jats:styled-content>\n (\n rmMIF<\/jats:styled-content>\n ) was given to\n MIF<\/jats:styled-content>\n \u2212\/\u2212<\/jats:sup>\n mice challenged with or without doxorubicin. Echocardiographic, cardiomyocyte function, and intracellular Ca\n 2+<\/jats:sup>\n handling were evaluated. Autophagy and apoptosis were examined. Mitochondrial morphology and function were examined using transmission electron microscopy,\n JC<\/jats:styled-content>\n \u20101 staining, Mito\n SOX<\/jats:styled-content>\n Red fluorescence, and mitochondrial respiration complex assay.\n DHE<\/jats:styled-content>\n staining was used to evaluate\n reactive oxygen species (ROS<\/jats:styled-content>\n ) generation.\n MIF<\/jats:styled-content>\n knockout exacerbated doxorubicin\u2010induced mortality and cardiomyopathy (compromised fractional shortening, cardiomyocyte and mitochondrial function, apoptosis, and\n ROS<\/jats:styled-content>\n generation). These detrimental effects of doxorubicin were accompanied by defective autophagolysosome formation, the effect of which was exacerbated by\n MIF<\/jats:styled-content>\n knockout. Rapamycin pretreatment rescued doxorubicin\u2010induced cardiomyopathy in\n WT<\/jats:styled-content>\n and\n MIF<\/jats:styled-content>\n \u2212\/\u2212<\/jats:sup>\n mice. Blocking autophagolysosome formation using BafA1 negated the cardioprotective effect of rapamycin and\n rmMIF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our data suggest that\n MIF<\/jats:styled-content>\n serves as an indispensable cardioprotective factor against doxorubicin\u2010induced cardiomyopathy with an underlying mechanism through facilitating autophagolysosome formation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.113.000439","type":"journal-article","created":{"date-parts":[[2013,12,13]],"date-time":"2013-12-13T04:06:51Z","timestamp":1386907611000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["Macrophage Migration Inhibitory Factor Deficiency Augments Doxorubicin\u2010Induced Cardiomyopathy"],"prefix":"10.1161","volume":"2","author":[{"given":"Xihui","family":"Xu","sequence":"first","affiliation":[{"name":"Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, School of Pharmacy, Laramie, WY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Bucala","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yale School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ren","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, School of Pharmacy, Laramie, WY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11407"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199809243391307"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.799700"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-009-0051-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.11.013"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0869"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.03.006"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7827(00)00005-9"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi971475e"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1200"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06504"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00189.2004"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-0407.2010.00088.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.110.953208"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39738"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.028"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03029"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1574"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5638"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015081108"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.842252"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27523"},{"key":"e_1_3_3_24_2","first-page":"A13562","article-title":"Autophagic changes in cardiomyocyte predict good prognosis for dilated cardiomyopathy","volume":"216","author":"Saito T","year":"2012","unstructured":"Saito T. 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