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 invitro and invivo. 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.
|Original language||English (US)|
|Number of pages||12|
|State||Published - Aug 2014|
Bibliographical noteFunding Information:
This study was funded by Global Innovative Research Center ( GiRC, 2012K1A1A2A01056095 ) program of National Research Foundation of Korea (NRF) and the Intramural Research Program of KIST.
Copyright 2014 Elsevier B.V., All rights reserved.
- Deoxycholic acid-modified polyethylenimine
- Myocardial ischemia-reperfusion injury
- RAGE siRNA
- SiRNA delivery