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Deoxycholic acid-modified polyethylenimine based nanocarriers for RAGE siRNA therapy in acute myocardial infarction
- Source :
- Archives of pharmacal research. 38(7)
- Publication Year :
- 2014
-
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.
- Subjects :
- Male
Cardiotonic Agents
endocrine system diseases
Receptor for Advanced Glycation End Products
Ischemia
Myocardial Infarction
Myocardial Reperfusion Injury
Pharmacology
RAGE (receptor)
Fibrosis
Glycation
RNA interference
Drug Discovery
Medicine
Animals
Polyethyleneimine
cardiovascular diseases
RNA, Small Interfering
Receptor
Drug Carriers
business.industry
Organic Chemistry
nutritional and metabolic diseases
Drug Synergism
medicine.disease
Blockade
Nanostructures
Rats
Anesthesia
cardiovascular system
Molecular Medicine
business
human activities
Reperfusion injury
Deoxycholic Acid
Subjects
Details
- ISSN :
- 19763786
- Volume :
- 38
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Archives of pharmacal research
- Accession number :
- edsair.doi.dedup.....c2276547d415bf8f08a26c8880e0e5fa