RAGE siRNA-mediated gene silencing provides cardioprotection against ventricular arrhythmias in acute ischemia and reperfusion

Hyelim Park, Sook Hee Ku, Hyewon Park, Jueun Hong, Dongkyu Kim, Bum Rak Choi, Hui Nam Pak, Moon Hyoung Lee, Hyejung Mok, Ji Hoon Jeong, Donghoon Choi, Sun Hwa Kim, Boyoung Joung

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Expression of receptor for advanced glycation end-products (RAGE) is suggested to play a crucial role in mediating cardiac ischemia/reperfusion (IR) injury, and the blockade of RAGE signaling has been considered as a potential therapeutic strategy for the treatment of IR-induced cardiac damage. In this study, we primarily investigated the effects of RAGE suppression particularly on IR-induced ventricular arrhythmia. To inhibit the IR-induced upregulation of RAGE, siRNA targeting RAGE (siRAGE) was delivered to myocardium by using deoxycholic acid-modified polyethylenimine (PEI-DA) as a non-viral gene carrier. The resultant PEI-DA/siRAGE nanocomplexes successfully silenced the expression of RAGE and attenuated the inflammation and apoptosis in the ischemic-reperfused myocardium. According to our results, the electrophysiological properties (e.g., action potential propagation, action potential duration, and conduction velocity), disrupted by IR injury, were restored to normal level and the induction of ventricular tachycardia was abolished by RAGE silencing. We further found that RAGE suppression led to the activation of Wnt signaling, followed by the expression of gap junction protein, connexin43. Thus it could be concluded that successful siRAGE delivery is protective against IR-induced ventricular arrhythmia.

Original languageEnglish
Article number7846
Pages (from-to)315-326
Number of pages12
JournalJournal of Controlled Release
Volume217
DOIs
Publication statusPublished - 2015 Nov 10

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Gene Silencing
Small Interfering RNA
Reperfusion
Cardiac Arrhythmias
Ischemia
Reperfusion Injury
Action Potentials
Myocardium
Polyethyleneimine
Connexin 43
Connexins
Deoxycholic Acid
Advanced Glycosylation End Product-Specific Receptor
Ventricular Tachycardia
Up-Regulation
Apoptosis
Inflammation
Genes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Park, Hyelim ; Ku, Sook Hee ; Park, Hyewon ; Hong, Jueun ; Kim, Dongkyu ; Choi, Bum Rak ; Pak, Hui Nam ; Lee, Moon Hyoung ; Mok, Hyejung ; Jeong, Ji Hoon ; Choi, Donghoon ; Kim, Sun Hwa ; Joung, Boyoung. / RAGE siRNA-mediated gene silencing provides cardioprotection against ventricular arrhythmias in acute ischemia and reperfusion. In: Journal of Controlled Release. 2015 ; Vol. 217. pp. 315-326.
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abstract = "Expression of receptor for advanced glycation end-products (RAGE) is suggested to play a crucial role in mediating cardiac ischemia/reperfusion (IR) injury, and the blockade of RAGE signaling has been considered as a potential therapeutic strategy for the treatment of IR-induced cardiac damage. In this study, we primarily investigated the effects of RAGE suppression particularly on IR-induced ventricular arrhythmia. To inhibit the IR-induced upregulation of RAGE, siRNA targeting RAGE (siRAGE) was delivered to myocardium by using deoxycholic acid-modified polyethylenimine (PEI-DA) as a non-viral gene carrier. The resultant PEI-DA/siRAGE nanocomplexes successfully silenced the expression of RAGE and attenuated the inflammation and apoptosis in the ischemic-reperfused myocardium. According to our results, the electrophysiological properties (e.g., action potential propagation, action potential duration, and conduction velocity), disrupted by IR injury, were restored to normal level and the induction of ventricular tachycardia was abolished by RAGE silencing. We further found that RAGE suppression led to the activation of Wnt signaling, followed by the expression of gap junction protein, connexin43. Thus it could be concluded that successful siRAGE delivery is protective against IR-induced ventricular arrhythmia.",
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RAGE siRNA-mediated gene silencing provides cardioprotection against ventricular arrhythmias in acute ischemia and reperfusion. / Park, Hyelim; Ku, Sook Hee; Park, Hyewon; Hong, Jueun; Kim, Dongkyu; Choi, Bum Rak; Pak, Hui Nam; Lee, Moon Hyoung; Mok, Hyejung; Jeong, Ji Hoon; Choi, Donghoon; Kim, Sun Hwa; Joung, Boyoung.

In: Journal of Controlled Release, Vol. 217, 7846, 10.11.2015, p. 315-326.

Research output: Contribution to journalArticle

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AU - Park, Hyelim

AU - Ku, Sook Hee

AU - Park, Hyewon

AU - Hong, Jueun

AU - Kim, Dongkyu

AU - Choi, Bum Rak

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AU - Lee, Moon Hyoung

AU - Mok, Hyejung

AU - Jeong, Ji Hoon

AU - Choi, Donghoon

AU - Kim, Sun Hwa

AU - Joung, Boyoung

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