title: Deoxycholic acid-modified polyethylenimine based nanocarriers for RAGE siRNA therapy in acute myocardial infarction.
abstract: The activation of receptor for advanced glycation end products (RAGE) signaling is mainly associated with myocardial ischemia/reperfusion injury. Thus the blockade of RAGE-ligands axis can be considered as a potential therapeutic strategy to protect myocardial infarction after ischemia/reperfusion injury. Herein, we strengthened the cardioprotective effect with combinatorial treatment of soluble RAGE (sRAGE) and RAGE siRNA (siRAGE) causing more effective suppression of RAGE-mediated signaling transduction. For pharmacological blockade of RAGE, sRAGE, the extracellular ligand binding domain of RAGE, acts as a pharmacological ligand decoy and inhibits the interaction between RAGE and its ligands. For genetic deletion of RAGE, siRAGE suppresses the expression of RAGE by participating in RNA interference mechanism. Therefore, we combined these two RAGE blockade/deletion strategies and investigated the therapeutic effects on rat ischemic and reperfused myocardium. According to our results, based on RAGE expression level analysis and infarct size/fibrosis measurement, co-treatment of sRAGE and siRAGE exhibited synergic cardioprotective effects; thus the newly designed regimen can be considered as a promising candidate for the treatment of myocardial infarction.
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea.
authors.forename: Sook Hee
authors.initials: SH
authors.lastname: Ku
authors.forename: Jueun
authors.initials: J
authors.lastname: Hong
authors.forename: Hyung-Ho
authors.initials: HH
authors.lastname: Moon
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Hyejung
authors.initials: H
authors.lastname: Mok
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.forename: Donghoon
authors.initials: D
authors.lastname: Choi
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004357:Drug Synergism; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics* / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000628:therapy; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use*; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C000593874:Ager protein, rat; D002316:Cardiotonic Agents; D004337:Drug Carriers; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; D003840:Deoxycholic Acid; D011094:Polyethyleneimine