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 2024-01-20T05:33:36Z 2024-01-20T05:33:36Z 2021-09-03 2015-11-10 0168-3659 https://pubs.kist.re.kr/handle/201004/124760 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. (c) 2015 Elsevier B.V. All rights reserved. English ELSEVIER GLYCATION END-PRODUCTS INFARCT SIZE RECEPTOR THERAPY INJURY WNT OVEREXPRESSION PROLIFERATION EXPRESSION CONDUCTION RAGE siRNA-mediated gene silencing provides cardioprotection against ventricular arrhythmias in acute ischemia and reperfusion Article 10.1016/j.jconrel.2015.09.006 1 JOURNAL OF CONTROLLED RELEASE, v.217, pp.315 - 326 JOURNAL OF CONTROLLED RELEASE 217 315 326 scie scopus 000363481500033 2-s2.0-84943193880 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article GLYCATION END-PRODUCTS INFARCT SIZE RECEPTOR THERAPY INJURY WNT OVEREXPRESSION PROLIFERATION EXPRESSION CONDUCTION Receptor for advanced glycation end-products siRNA Ischemia/reperfusion injury Arrhythmia Connexin43 Wnt1