title: Cardiac RNAi therapy using RAGE siRNA/deoxycholic acid-modified polyethylenimine complexes for myocardial infarction.
abstract: 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.
authors.affiliation: Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University Health System, Seoul 120-752, Republic of Korea; Korea Testing & Research Institue (KTR), 155 Beodeunaru-ro, Yeongdeungpo-gu, Seoul 150-038, Republic of Korea.
authors.forename: Jueun
authors.initials: J
authors.lastname: Hong
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea.
authors.forename: Sook Hee
authors.initials: SH
authors.lastname: Ku
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Min Sang
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hyejung
authors.initials: H
authors.lastname: Mok
authors.affiliation: Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University Health System, Seoul 120-752, Republic of Korea. Electronic address: cdhlyj@yuhs.ac.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Choi
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, Republic of Korea. Electronic address: sunkim@kist.re.kr.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011094:Polyethyleneimine / Q000031:analogs & derivatives*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D003840:Deoxycholic Acid; D011094:Polyethyleneimine
keywords: Deoxycholic acid-modified polyethylenimine; Myocardial ischemia-reperfusion injury; RAGE siRNA; siRNA delivery