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KMID : 0043320150380071317
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Archives of Pharmacal Research
2015 Volume.38 No. 7 p.1317 ~ p.1324
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Deoxycholic acid-modified polyethylenimine based nanocarriers for RAGE siRNA therapy in acute myocardial infarction
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Ku Sook-Hee
Hong Ju-Eun
Moon Hyung-Ho
Jeong Ji-Hoon
Mok Hye-Jung
Park Sung-Ha
Choi Dong-Hoon
Kim Sun-Hwa
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Abstract
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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.
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KEYWORD
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Myocardial ischemia, Soluble RAGE, RAGE siRNA, Combination therapy
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