{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:19:02Z","timestamp":1793049542670,"version":"4.5.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Elamipretide (MTP-131), a novel mitochondria-targeting peptide, was shown to reduce infarct size in animals with myocardial infarction and improve renal function in pigs with acute and chronic kidney injury. This study examined the effects of chronic therapy with elamipretide on left ventricular (LV) and mitochondrial function in dogs with heart failure (HF).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Fourteen dogs with microembolization-induced HF were randomized to 3 months monotherapy with subcutaneous injections of elamipretide (0.5 mg\/kg once daily, HF+ELA, n=7) or saline (control, HF-CON, n=7). LV ejection fraction, plasma n-terminal pro-brain natriuretic peptide, tumor necrosis factor-\u03b1, and C-reactive protein were measured before (pretreatment) and 3 months after initiating therapy (post-treatment). Mitochondrial respiration, membrane potential (\u0394\u03c8m), maximum rate of ATP synthesis, and ATP\/ADP ratio were measured in isolated LV cardiomyocytes obtained at post-treatment. In HF-CON dogs, ejection fraction decreased at post-treatment compared with pretreatment (29\u00b11% versus 31\u00b12%), whereas in HF+ELA dogs, ejection fraction significantly increased at post-treatment compared with pretreatment (36\u00b12% versus 30\u00b12%;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). In HF-CON, n-terminal pro-brain natriuretic peptide increased by 88\u00b1120 pg\/mL during follow-up but decreased significantly by 774\u00b185 pg\/mL in HF+ELA dogs (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Treatment with elamipretide also normalized plasma tumor necrosis factor-\u03b1 and C-reactive protein and restored mitochondrial state-3 respiration, \u0394\u03c8m, rate of ATP synthesis, and ATP\/ADP ratio (ATP\/ADP: 0.38\u00b10.04 HF-CON versus 1.16\u00b10.15 HF+ELA;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Long-term therapy with elamipretide improves LV systolic function, normalizes plasma biomarkers, and reverses mitochondrial abnormalities in LV myocardium of dogs with advanced HF. The results support the development of elamipretide for the treatment of HF.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.115.002206","type":"journal-article","created":{"date-parts":[[2018,9,30]],"date-time":"2018-09-30T07:20:59Z","timestamp":1538292059000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":193,"title":["Chronic Therapy With Elamipretide (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular and Mitochondrial Function in Dogs With Advanced Heart Failure"],"prefix":"10.1161","volume":"9","author":[{"given":"Hani N.","family":"Sabbah","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh C.","family":"Gupta","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita","family":"Kohli","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjun","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souheila","family":"Hachem","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefei","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.097782"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.07.005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.112.001644"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.199919"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2828(92)93098-5"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0739"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.09.013"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2000.1266"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.040147"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200906098"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.330167"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2015.03.007"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402999200"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012121216"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000406"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010080808"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00471.2013"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/ARS.2009.2445"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/1074248413508003"},{"issue":"4","key":"e_1_3_3_21_2","first-page":"H1379","article-title":"A canine model of chronic heart failure produced by multiple sequential coronary microembolizations.","volume":"260","author":"Sabbah HN","year":"1991","unstructured":"Sabbah HN, Stein PD, Kono T, Gheorghiade M, Levine TB, Jafri S, Hawkins ET, Goldstein S. 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