Therapeutic Cardiac-Targeted Delivery of miR-1 Reverses Pressure Overload-Induced Cardiac Hypertrophy and Attenuates Pathological Remodeling
DC Field | Value | Language |
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dc.contributor.author | Karakikes, Ioannis | - |
dc.contributor.author | Chaanine, Antoine H. | - |
dc.contributor.author | Kang, Soojeong | - |
dc.contributor.author | Mukete, Bertrand N. | - |
dc.contributor.author | Jeong, Dongtak | - |
dc.contributor.author | Zhang, Shihong | - |
dc.contributor.author | Hajjar, Roger J. | - |
dc.contributor.author | Lebeche, Djamel | - |
dc.date.accessioned | 2021-06-23T03:44:20Z | - |
dc.date.available | 2021-06-23T03:44:20Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2013-04 | - |
dc.identifier.issn | 2047-9980 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/28458 | - |
dc.description.abstract | Background-MicroRNAs (miRNAs) play a key role in the development of heart failure, and recent studies have shown that the muscle-specific miR-1 is a key regulator of cardiac hypertrophy. We tested the hypothesis that chronic restoration of miR-1 gene expression in vivo will regress hypertrophy and protect against adverse cardiac remodeling induced by pressure overload. Methods and Results-Cardiac hypertrophy was induced by left ventricular pressure overload in male Sprague-Dawley rats subjected to ascending aortic stenosis. When the hypertrophy was established at 2 weeks after surgery, the animals were randomized to receive either an adeno-associated virus expressing miR-1 (AAV9.miR-1) or green fluorescent protein (GFP) as control (AAV9.GFP) via a single-bolus tail-vein injection. Administration of miR-1 regressed cardiac hypertrophy (left ventricular posterior wall thickness,; 2.32 +/- 0.08 versus 2.75 +/- 0.07 mm, P<0.001) and (left ventricular septum wall thickness, 2.23 +/- 0.06 versus 2.54 +/- 0.10 mm, P<0.05) and halted the disease progression compared with control-treated animals, as assessed by echocardiography (fractional shortening, 37.60 +/- 5.01% versus 70.68 +/- 2.93%, P<0.05) and hemodynamic analyses (end-systolic pressure volume relationship/effective arterial elastance, 1.87 +/- 0.46 versus 0.96 +/- 0.38, P<0.05) after 7 weeks of treatment. Additionally, miR-1 replacement therapy lead to a marked reduction of myocardial fibrosis, an improvement in calcium handling, inhibition of apoptosis, and inactivation of the mitogen-activated 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 miR-1, Fibullin-2 (Fbln2), a secreted protein implicated in extracellular matrix remodeling. Conclusions-Taken together, our findings suggest that restoration of miR-1 gene expression is a potential novel therapeutic strategy to reverse pressure-induced cardiac hypertrophy and prevent maladaptive cardiac remodeling. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.title | Therapeutic Cardiac-Targeted Delivery of miR-1 Reverses Pressure Overload-Induced Cardiac Hypertrophy and Attenuates Pathological Remodeling | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jeong, Dongtak | - |
dc.identifier.doi | 10.1161/JAHA.113.000078 | - |
dc.identifier.scopusid | 2-s2.0-84880816481 | - |
dc.identifier.wosid | 000326338400014 | - |
dc.identifier.bibliographicCitation | JOURNAL OF THE AMERICAN HEART ASSOCIATION, v.2, no.2, pp.1 - 16 | - |
dc.relation.isPartOf | JOURNAL OF THE AMERICAN HEART ASSOCIATION | - |
dc.citation.title | JOURNAL OF THE AMERICAN HEART ASSOCIATION | - |
dc.citation.volume | 2 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 16 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cardiovascular System & Cardiology | - |
dc.relation.journalWebOfScienceCategory | Cardiac & Cardiovascular Systems | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | HEART-FAILURE | - |
dc.subject.keywordPlus | SIGNALING PATHWAYS | - |
dc.subject.keywordPlus | MICRORNAS | - |
dc.subject.keywordPlus | FIBULIN-2 | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | TISSUE | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | DYSREGULATION | - |
dc.subject.keywordPlus | CONDUCTANCE | - |
dc.subject.keywordAuthor | gene therapy | - |
dc.subject.keywordAuthor | hypertrophy/remodeling | - |
dc.subject.keywordAuthor | left ventricular hypertrophy | - |
dc.subject.keywordAuthor | left ventricular remodeling | - |
dc.subject.keywordAuthor | microRNA | - |
dc.identifier.url | https://www.ahajournals.org/doi/10.1161/JAHA.113.000078 | - |
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