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Cardiac RNAi therapy using RAGE siRNA/deoxycholic acid-modified polyethylenimine complexes for myocardial infarction

 Jueun Hong  ;  Sook Hee Ku  ;  Min Sang Lee  ;  Ji Hoon Jeong  ;  Hyejung Mok  ;  Donghoon Choi  ;  Sun Hwa Kim 
 BIOMATERIALS, Vol.35(26) : 7562-7573, 2014 
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Animals ; Cell Line ; Deoxycholic Acid/analogs & derivatives* ; Male ; Myocardial Reperfusion Injury/genetics ; Myocardial Reperfusion Injury/pathology ; Myocardial Reperfusion Injury/therapy* ; Myocardium/metabolism ; Myocardium/pathology ; Polyethyleneimine/analogs & derivatives* ; RNA Interference* ; RNA, Small Interfering/administration & dosage* ; RNA, Small Interfering/genetics ; Rats ; Rats, Sprague-Dawley ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic/genetics* ; Transfection*
Deoxycholic acid-modified polyethylenimine ; Myocardial ischemia-reperfusion injury ; RAGE siRNA ; siRNA delivery
Inflammatory response in myocardial ischemia-reperfusion injury plays a critical role in ventricular remodeling. To avoid deleterious effects of overwhelming inflammation, we blocked the expression of receptor for advanced glycation end-products (RAGE), a key mediator of the local and systemic inflammatory responses, via RNAi mechanism. Herein, a facial amphipathic deoxycholic acid-modified low molecular weight polyethylenimine (DA-PEI) was used as a siRNA delivery carrier to myocardium. The DA-PEI conjugate formed a stable complex with siRNA via electrostatic and hydrophobic interactions. The siRAGE/DA-PEI formulation having negligible toxicity could enhance intracellular delivery efficiency and successfully suppress RAGE expression both in vitro and in vivo. Furthermore, the cardiac administration of siRAGE/DA-PEI reduced apoptosis and inflammatory cytokine release, subsequently led to attenuation of left ventricular remodeling in rat myocardial infarction model. The potential therapeutic effects of RAGE gene silencing on myocardial ischemia-reperfusion injury may suggest that the siRAGE/DA-PEI delivery system can be considered as a promising strategy for treating myocardial infarction.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Choi, Dong Hoon(최동훈) ORCID logo https://orcid.org/0000-0002-2009-9760
Hong, Ju Eun(홍주은)
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