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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 FieldValueLanguage
dc.contributor.author김동규-
dc.contributor.author문형호-
dc.contributor.author최동훈-
dc.contributor.author홍주은-
dc.date.accessioned2014-12-18T09:33:36Z-
dc.date.available2014-12-18T09:33:36Z-
dc.date.issued2013-
dc.identifier.issn0168-3659-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/88397-
dc.description.abstractThe 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.statementOfResponsibilityopen-
dc.relation.isPartOfJournal of Controlled Release-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleAnti-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.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorDongkyu Kim-
dc.contributor.googleauthorJueun Hong-
dc.contributor.googleauthorHyung-Ho Moon-
dc.contributor.googleauthorHye Yeong Nam-
dc.contributor.googleauthorHyejung Mok-
dc.contributor.googleauthorJi Hoon Jeong-
dc.contributor.googleauthorSung Wan Kim-
dc.contributor.googleauthorDonghoon Choi-
dc.contributor.googleauthorSun Hwa Kim-
dc.identifier.doi10.1016/j.jconrel.2013.02.031-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00397-
dc.contributor.localIdA01392-
dc.contributor.localIdA04053-
dc.contributor.localIdA04437-
dc.relation.journalcodeJ01352-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0168365913001442-
dc.contributor.alternativeNameKim, Dong Kyu-
dc.contributor.alternativeNameMoon, Hyung Ho-
dc.contributor.alternativeNameChoi, Dong Hoon-
dc.contributor.alternativeNameHong, Ju Eun-
dc.contributor.affiliatedAuthorKim, Dong Kyu-
dc.contributor.affiliatedAuthorMoon, Hyung Ho-
dc.contributor.affiliatedAuthorChoi, Dong Hoon-
dc.contributor.affiliatedAuthorHong, Ju Eun-
dc.rights.accessRightsnot free-
dc.citation.volume168-
dc.citation.number2-
dc.citation.startPage125-
dc.citation.endPage134-
dc.identifier.bibliographicCitationJournal of Controlled Release, Vol.168(2) : 125-134, 2013-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

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