{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T07:01:49Z","timestamp":1784617309587,"version":"3.55.0"},"reference-count":46,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["5R01HL092141"],"award-info":[{"award-number":["5R01HL092141"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["5R01HL093579"],"award-info":[{"award-number":["5R01HL093579"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["1U24 HL094373"],"award-info":[{"award-number":["1U24 HL094373"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["1R01 HL11657"],"award-info":[{"award-number":["1R01 HL11657"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:p> Oxidative stress results in mtDNA damage and contributes to myocardial cell death. mtDNA repair enzymes are crucial for mtDNA repair and cell survival. We investigated a novel, mitochondria-targeted fusion protein (Exscien1-III) containing endonuclease III in myocardial ischemia-reperfusion injury and transverse aortic constriction (TAC)-induced heart failure. Male C57\/BL6J mice (10\u201312 wk) were subjected to 45 min of myocardial ischemia and either 24 h or 4 wk of reperfusion. Exscien1-III (4 mg\/kg ip) or vehicle was administered at the time of reperfusion. Male C57\/BL6J mice were subjected to TAC, and Exscien1-III (4 mg\/kg i.p) or vehicle was administered daily starting at 3 wk post-TAC and continued for 12 wk. Echocardiography was performed to assess left ventricular (LV) structure and function. Exscien1-III reduced myocardial infarct size ( P &lt; 0.01) at 24 h of reperfusion and preserved LV ejection fraction at 4 wk postmyocardial ischemia. Exscien1-III attenuated TAC-induced LV dilation and dysfunction at 6\u201312 wk post-TAC ( P &lt; 0.05). Exscien1-III reduced ( P &lt; 0.05) cardiac hypertrophy and maladaptive remodeling after TAC. Assessment of cardiac mitochondria showed that Exscien1-III localized to mitochondria and increased mitochondrial antioxidant and reduced apoptotic markers. In conclusion, our results indicate that administration of Exscien1-III provides significant protection against myocardial ischemia and preserves myocardial structure and LV performance in the setting of heart failure. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Oxidative stress-induced mitochondrial DNA damage is a prominent feature in the pathogenesis of cardiovascular diseases. In the present study, we demonstrate the efficacy of a novel, mitochondria-targeted fusion protein that traffics endonuclease III specifically for mitochondrial DNA repair in two well-characterized murine models of cardiac injury and failure. <\/jats:p>","DOI":"10.1152\/ajpheart.00515.2017","type":"journal-article","created":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T09:46:59Z","timestamp":1512553619000},"page":"H311-H321","source":"Crossref","is-referenced-by-count":24,"title":["A novel mtDNA repair fusion protein attenuates maladaptive remodeling and preserves cardiac function in heart failure"],"prefix":"10.1152","volume":"314","author":[{"given":"Jessica M.","family":"Bradley","sequence":"first","affiliation":[{"name":"Cardiovascular Center of Excellence and Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence and Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea L.","family":"Organ","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence and Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Polhemus","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence and Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence and Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazi N.","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashi","family":"Bhushan","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence and Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olena M.","family":"Gorodnya","sequence":"additional","affiliation":[{"name":"College of Medicine, University of South Alabama, Mobile, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykhaylo V.","family":"Ruchko","sequence":"additional","affiliation":[{"name":"College of Medicine, University of South Alabama, Mobile, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark N.","family":"Gillespie","sequence":"additional","affiliation":[{"name":"College of Medicine, University of South Alabama, Mobile, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn L.","family":"Wilson","sequence":"additional","affiliation":[{"name":"College of Medicine, University of South Alabama, Mobile, Alabama"},{"name":"Exscien Corporation, Mobile, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Lefer","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence and Department of Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2007.09.005"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.301475"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00343.2013"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00163.2015"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0789"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.12.2527"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00210.2011"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2012.06.002"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.23.3071"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.41.25409"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-8777(99)00025-7"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.12.044"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr274"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00443.2001"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000831200"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705891104"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.670588"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2001.280.6.L1300"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413022200"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00071.2012"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/ph7080894"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.88.5.529"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.11.1107"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.515130"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051627098"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000855"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(03)00084-1"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9782"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1378"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-376"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2940"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.7.1506"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nature10992"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.04.011"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-016-9536-9"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000299"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh648"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.10.692"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2005.03.002"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.3.H1422"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-012-0305-4"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.08.109"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00157.2011"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405844200"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2008.03.012"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-014-0459-0"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00515.2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T18:25:32Z","timestamp":1569954332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00515.2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,1]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2,1]]}},"alternative-id":["10.1152\/ajpheart.00515.2017"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00515.2017","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,1]]}}}