A Soluble Epoxide Hydrolase Inhibitor Upregulated KCNJ12 and KCNIP2 by Downregulating MicroRNA-29 in a Mouse Model of Myocardial Infarction

Authors

  • Xiao-Jun Zhang Department of Internal Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha
  • Cai-Xiu Liao Department of Geratology, The Third Hospital of Changsha, Changsha, Hunan, China
  • Kai-Jun Sun Department of Internal Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha
  • Lei-Ling Liu Department of Internal Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha
  • Dan-Yan Xu Department of Internal Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha

DOI:

https://doi.org/10.1532/hsf.2999

Keywords:

Soluble epoxide hydrolase inhibitors, miR-29, Ischemic arrhythmia

Abstract

Background: Soluble epoxide hydrolase inhibitors (sEHi) have anti-arrhythmic effects, and we previously found that the novel sEHi t-AUCB (trans-4[-4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid) significantly inhibited ventricular arrhythmias after myocardial infarction (MI). However, the mechanism is unknown. It’s known that microRNA-29 (miR-29) participates in the occurrence of arrhythmias. In this study, we investigated whether sEHi t-AUCB was protective against ischemic arrhythmias by modulating miR-29 and its target genes KCNJ12 and KCNIP2.

Methods: Male 8-week-old C57BL/6 mice were divided into five groups and fed distilled water only or distilled water with t-AUCB of different dosages for seven days. Then, the mice underwent MI or sham surgery. The ischemic region of the myocardium was obtained 24 hours after MI to detect miR-29, KCNJ12, and KCNIP2 mRNA expression levels via real-time PCR and KCNJ12 and KCNIP2 protein expression levels via western blotting.

Results: MiR-29 expression levels were significantly increased in the ischemic region of MI mouse hearts and the mRNA and protein expression levels of its target genes KCNJ12 and KCNIP2 were significantly decreased. T-AUCB prevented these changes dose-dependently.

Conclusion: The sEHi t-AUCB regulates the expression levels of miR-29 and its target genes KCNJ12 and KCNIP2, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmia.

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Published

2020-08-12

How to Cite

Zhang, X., Liao, C., Sun, K., Liu, L. ., & Xu, D. (2020). A Soluble Epoxide Hydrolase Inhibitor Upregulated KCNJ12 and KCNIP2 by Downregulating MicroRNA-29 in a Mouse Model of Myocardial Infarction. The Heart Surgery Forum, 23(5), E579-E585. https://doi.org/10.1532/hsf.2999

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Articles