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: Sook Hee Ku, Jueun Hong, Hyung-Ho Moon, Ji Hoon Jeong, Hyejung Mok, Sungha Park, Donghoon Choi, Sun Hwa Kim
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 38 Issue 7 Pg. 1317-24 (Jul 2015) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 25559468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ager protein, rat
• Cardiotonic Agents
• Drug Carriers
• RNA, Small Interfering
• Receptor for Advanced Glycation End Products
• Deoxycholic Acid
• Polyethyleneimine

Topics

• Animals
• Cardiotonic Agents (administration & dosage)
• Deoxycholic Acid (administration & dosage, chemistry)
• Drug Carriers (administration & dosage, chemistry)
• Drug Synergism
• Male
• Myocardial Infarction (genetics, therapy)
• Myocardial Reperfusion Injury (genetics, therapy)
• Nanostructures (administration & dosage, chemistry)
• Polyethyleneimine (administration & dosage, chemistry)
• RNA, Small Interfering (administration & dosage, genetics, therapeutic use)
• Rats
• Receptor for Advanced Glycation End Products (antagonists & inhibitors, genetics, metabolism)