{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:22:37Z","timestamp":1793384557455,"version":"4.5.0"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2013,3,12]]},"abstract":"\n Background<\/jats:title>\n \n Micro\n RNA<\/jats:styled-content>\n s (mi\n RNA<\/jats:styled-content>\n s) play a key role in the development of heart failure, and recent studies have shown that the muscle\u2010specific\n miR\u20101<\/jats:italic>\n is a key regulator of cardiac hypertrophy. We tested the hypothesis that chronic restoration of\n miR\u20101<\/jats:italic>\n gene expression in vivo will regress hypertrophy and protect against adverse cardiac remodeling induced by pressure overload.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Cardiac hypertrophy was induced by left ventricular pressure overload in male\n S<\/jats:styled-content>\n prague\u2010\n D<\/jats:styled-content>\n awley rats subjected to ascending aortic stenosis. When the hypertrophy was established at 2\u00a0weeks after surgery, the animals were randomized to receive either an adeno\u2010associated virus expressing\n miR\u20101<\/jats:italic>\n (\n AAV<\/jats:styled-content>\n 9.\n miR\u20101<\/jats:italic>\n ) or green fluorescent protein (\n GFP<\/jats:styled-content>\n ) as control (\n AAV<\/jats:styled-content>\n 9.\n \n GFP<\/jats:styled-content>\n <\/jats:italic>\n ) via a single\u2010bolus tail\u2010vein injection. Administration of\n miR\u20101<\/jats:italic>\n regressed cardiac hypertrophy (left ventricular posterior wall thickness,; 2.32\u00b10.08 versus 2.75\u00b10.07\u00a0mm,\n P<\/jats:italic>\n <0.001) and (left ventricular septum wall thickness, 2.23\u00b10.06\u00a0versus 2.54\u00b10.10\u00a0mm,\n P<\/jats:italic>\n <0.05) and halted the disease progression compared with control\u2010treated animals, as assessed by echocardiography (fractional shortening, 37.60\u00b15.01% versus 70.68\u00b12.93%,\n P<\/jats:italic>\n <0.05) and hemodynamic analyses (end\u2010systolic pressure volume relationship\/effective arterial elastance, 1.87\u00b10.46 versus 0.96\u00b10.38,\n P<\/jats:italic>\n <0.05) after 7\u00a0weeks of treatment. Additionally,\n miR\u20101<\/jats:italic>\n replacement therapy lead to a marked reduction of myocardial fibrosis, an improvement in calcium handling, inhibition of apoptosis, and inactivation of the mitogen\u2010activated protein kinase signaling pathways, suggesting a favorable effect on preventing the maladaptive ventricular remodeling. We also identified and validated a novel bona fide target of\n miR\u20101<\/jats:italic>\n , Fibullin\u20102 (\n Fbln2<\/jats:italic>\n ), a secreted protein implicated in extracellular matrix remodeling.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Taken together, our findings suggest that restoration of\n miR\u20101<\/jats:italic>\n gene expression is a potential novel therapeutic strategy to reverse pressure\u2010induced cardiac hypertrophy and prevent maladaptive cardiac remodeling.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.113.000078","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T12:49:31Z","timestamp":1369399771000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":236,"title":["Therapeutic Cardiac\u2010Targeted Delivery of\n miR\u20101<\/i>\n Reverses Pressure Overload\u2013Induced Cardiac Hypertrophy and Attenuates Pathological Remodeling"],"prefix":"10.1161","volume":"2","author":[{"given":"Ioannis","family":"Karakikes","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine H.","family":"Chaanine","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soojeong","family":"Kang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand N.","family":"Mukete","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongtak","family":"Jeong","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J.","family":"Hajjar","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djamel","family":"Lebeche","sequence":"additional","affiliation":[{"name":"Graduate School of Biological Sciences, Mount Sinai School of Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199910213411706"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.59.1.551"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-114-5-345"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2193"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1328"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.09.009"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.183087"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33099"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng865"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000257913.42552.23"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1582"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.030"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.061170"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.687947"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608791103"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00144.2007"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01222-08"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.879429"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00035.2001"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.783852"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.138"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.91322.2008"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(97)78778-2"},{"issue":"1","key":"e_1_3_3_26_2","first-page":"I43","article-title":"Functional interplay between dual site phospholambam phosphorylation: insights from genetically altered mouse models","volume":"97","author":"Chu G","year":"2002","unstructured":"Chu G, Kranias EG. Functional interplay between dual site phospholambam phosphorylation: insights from genetically altered mouse models. Basic Res Cardiol. 2002;97(suppl 1):I43\u2013I48.","journal-title":"Basic Res Cardiol"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio1301"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.391"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq308"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07511"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.182535"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805038105"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.23.3071"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs043"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.067165"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm995"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1995.1003"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.1172"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.11.001"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09267"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03315"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.183426"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07228"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07242"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000237661.18885.f6"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2008.123"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01906668"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.62.4.757"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1996.0014"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.12.001"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/415198a"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114429"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.72.2.463"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.75.3.434"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh1101.091193"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.75.3.443"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.5.641"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.651bd.x"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.113.000078","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:51:49Z","timestamp":1715583109000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.113.000078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,12]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,3,12]]}},"alternative-id":["10.1161\/JAHA.113.000078"],"URL":"https:\/\/doi.org\/10.1161\/jaha.113.000078","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,12]]},"assertion":[{"value":"2012-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-02-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-04-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e000078"}}