title: Knockdown of EMMPRIN improves adverse remodeling mediated by IL-18 in the post-infarcted heart.
abstract: Interleukin-18 (IL-18) exacerbates cardiac dysfunction following myocardial infarction (MI). Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to exacerbate ventricular remodeling via induction of extracellular matrix metalloproteinase (MMP) synthesis. While up-regulation of EMMPRIN expression by IL-18 has been demonstrated in vitro, little is known regarding its in vivo effects. Here, we investigated the role of EMMPRIN in progressive post-infarct ventricular remodeling induced by IL-18. Cardiac function was impaired on echocardiography and organ weight was increased in mice receiving daily intraperitoneal injection of IL-18 following MI. Accompanying these adverse functional effect were increased EMMPRIN levels. Gene silencing of cardiac EMMPRIN by intramyocardial RNA interference rescued IL-18 mediated adverse effects on post-infarct cardiac function. Finally, EMMPRIN silencing reduced MMP-9 expression in the post-infarcted left ventricular myocardium. In conclusion, progressive post-infarct left ventricular remodeling induced by IL-18 can be reversed by gene silencing of EMMPRIN. Knock down of EMMPRIN may be a potential therapeutic strategy to abrogate the adverse effects of IL-18 on post-infarct left ventricular remodeling likely via MMP-9 inhibition.
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou, China.
authors.forename: Zizhuo
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou, China.
authors.forename: Rongjie
authors.initials: R
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou, China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Shu
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou, China.
authors.forename: Ruqiong
authors.initials: R
authors.lastname: Nie
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Guangzhou, China ; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou, China.
authors.forename: Shuanglun
authors.initials: S
authors.lastname: Xie
keywords: Interleukin-18; extracellular matrix metalloproteinase inducer; myocardial infarction; ventricular remodeling