Cited 44 times in
Anti-apoptotic cardioprotective effects of SHP-1 gene silencing against ischemia–reperfusion injury: Use of deoxycholic acid-modified low molecular weight polyethyleneimine as a cardiac siRNA-carrier
DC Field | Value | Language |
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dc.contributor.author | 김동규 | - |
dc.contributor.author | 문형호 | - |
dc.contributor.author | 최동훈 | - |
dc.contributor.author | 홍주은 | - |
dc.date.accessioned | 2014-12-18T09:33:36Z | - |
dc.date.available | 2014-12-18T09:33:36Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/88397 | - |
dc.description.abstract | The cardiomyocyte apoptosis plays a critical role in the development of myocardial injury after ischemia and reperfusion. Thus, alteration of the major apoptosis-regulatory factors during myocardial ischemia-reperfusion is expected to have favorable cardioprotective effects. Herein, we report ischemic-reperfused myocardial infarction (MI) repair with siRNA against Src homology region 2 domain-containing tyrosine phosphatase-1 (SHP-1), which is known as a key factor involved in regulating the progress of apoptosis in many cell types. A low molecular weight polyethyleneimine modified with deoxycholic acid (PEI1.8-DA)-based delivery strategy was suggested for the cardiac application of SHP-1 siRNA to overcome the poor gene delivery efficiency to myocardium due to the highly charged structures of the compact cardiac muscles. The PEI1.8-DA conjugates formed stable nanocomplexes with SHP-1 siRNA via electrostatic and hydrophobic interactions. The PEI1.8-DA/SHP-1 siRNA polyplexes effectively silenced SHP-1 gene expression in cardiomyocytes, leading to a significant inhibition of cardiomyocyte apoptosis under hypoxia. In comparison to conventional gene carriers, relatively large amounts of siRNA molecules remained after treatment with the PEI1.8-DA/SHP-1 siRNA polyplexes. Cardiac administration of the PEI1.8-DA/SHP-1 siRNA polyplexes resulted in substantial improvement in SHP-1 gene silencing, which can be explained by the enhancement of cardiac delivery efficiency of the PEI1.8-DA conjugates. In addition, in vivo treatment with the PEI1.8-DA/SHP-1 siRNA polyplexes induced a highly significant reduction in myocardial apoptosis and infarct size in rat MI models. These results demonstrate that the PEI1.8-DA/SHP-1 siRNA polyplex formulation is a useful system for efficient gene delivery into the compact myocardium that provides a fundamental advantage in treating ischemic-reperfused MI. | - |
dc.description.statementOfResponsibility | open | - |
dc.relation.isPartOf | JOURNAL OF CONTROLLED RELEASE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Anti-apoptotic cardioprotective effects of SHP-1 gene silencing against ischemia–reperfusion injury: Use of deoxycholic acid-modified low molecular weight polyethyleneimine as a cardiac siRNA-carrier | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Dongkyu Kim | - |
dc.contributor.googleauthor | Jueun Hong | - |
dc.contributor.googleauthor | Hyung-Ho Moon | - |
dc.contributor.googleauthor | Hye Yeong Nam | - |
dc.contributor.googleauthor | Hyejung Mok | - |
dc.contributor.googleauthor | Ji Hoon Jeong | - |
dc.contributor.googleauthor | Sung Wan Kim | - |
dc.contributor.googleauthor | Donghoon Choi | - |
dc.contributor.googleauthor | Sun Hwa Kim | - |
dc.identifier.doi | 10.1016/j.jconrel.2013.02.031 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00397 | - |
dc.contributor.localId | A01392 | - |
dc.contributor.localId | A04053 | - |
dc.contributor.localId | A04437 | - |
dc.relation.journalcode | J01352 | - |
dc.identifier.eissn | 1873-4995 | - |
dc.identifier.pmid | SHP-1 siRNA ; Myocardial apoptosis ; Deoxycholic acid ; Low molecular weight PEI ; Myocardial ischemia–reperfusion injury | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S0168365913001442 | - |
dc.subject.keyword | SHP-1 siRNA | - |
dc.subject.keyword | Myocardial apoptosis | - |
dc.subject.keyword | Deoxycholic acid | - |
dc.subject.keyword | Low molecular weight PEI | - |
dc.subject.keyword | Myocardial ischemia–reperfusion injury | - |
dc.contributor.alternativeName | Kim, Dong Kyu | - |
dc.contributor.alternativeName | Moon, Hyung Ho | - |
dc.contributor.alternativeName | Choi, Dong Hoon | - |
dc.contributor.alternativeName | Hong, Ju Eun | - |
dc.contributor.affiliatedAuthor | Kim, Dong Kyu | - |
dc.contributor.affiliatedAuthor | Moon, Hyung Ho | - |
dc.contributor.affiliatedAuthor | Choi, Dong Hoon | - |
dc.contributor.affiliatedAuthor | Hong, Ju Eun | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 168 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 125 | - |
dc.citation.endPage | 134 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CONTROLLED RELEASE, Vol.168(2) : 125-134, 2013 | - |
dc.identifier.rimsid | 32488 | - |
dc.type.rims | ART | - |
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