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

Title
RAGE siRNA-mediated gene silencing provides cardioprotection against ventricular arrhythmias in acute ischemia and reperfusion
Authors
박혜림구숙희박해원홍주은김동규최범락박휘남이문형목혜정정지훈최동훈김선화정보영
Keywords
Receptor for advanced glycation end-products; Ischemia/reperfusion injury; siRNA; Arrhythmia; Connexin43; Wnt1
Issue Date
2015-11
Publisher
Journal of controlled release
Citation
VOL 217, NO 10, 315-316
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 IRinduced 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.
URI
http://pubs.kist.re.kr/handle/201004/50810
ISSN
01683659
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KIST Publication > Article
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