Downregulation of DEC1 by RNA interference attenuates ischemia/reperfusion-induced myocardial inflammation by inhibiting the TLR4/NF-κB signaling pathway.

Abstract

Inflammation has been implicated in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury (MIRI). Previous studies have confirmed that deleted in esophageal cancer 1 (DEC1) is an important transcription factor in inflammation. However, the role of DEC1 in MIRI remains unclear. The present study aimed to determine whether the downregulation of DEC1 by RNA interference alleviated inflammation to protect against MIRI. Adult Sprague-Dawley rats (n=48) were randomly divided into four groups: Sham; I/R; adenovirus expressing green fluorescent protein control (Ad-G-Control); and DEC1-targeting RNA interference (Ad-G-DEC1) groups. Following gene delivery 4 days later, the rat myocardial I/R model was established and myocardial enzymes [creatine kinase (CK) and lactate dehydrogenase (LDH)] were detected. Hematoxylin and eosin (H&E) staining was performed to evaluate the myocardial damage and the infarct area was assessed using Evans Blue/triphenyltetrazolium chloride staining. The inflammatory mediators interleukin (IL)-β and tumor necrosis factor (TNF)-α were also detected using ELISA kits to assess the inflammatory response. Finally, western blotting and reverse transcription-quantitative PCR were used to analyze the expression levels of associated proteins and mRNAs. Ad-G-DEC1 RNA interference markedly decreased DEC1 expression levels. In addition, following the downregulation of DEC1 expression, the infarct size, CK, LDH, Toll-like receptor (TLR)4, NF-κB, IL-β and TNF-α levels were all significantly decreased. In conclusion, the results of the present study suggested that the downregulation of DEC1 may decrease the inflammation by suppressing the TLR4/NF-κB signaling pathway, which may represent a therapeutic target for MIRI.

• Authors: Weipan Xu, Kai Zhang, Yi Zhang, Shanxue Ma, Daoqun Jin
• Journal: Experimental and therapeutic medicine (Exp Ther Med) Vol. 20 Issue 1 Pg. 343-350 (Jul 2020) ISSN: 1792-0981 [Print] Greece
• PMID: 32537000 (Publication Type: Journal Article)
• Copyright: Copyright: © Xu et al.