scholarly journals Soluble epoxide hydrolase inhibitors, t-AUCB, regulated microRNA-1 and its target genes in myocardial infarction mice

Oncotarget ◽  
2017 ◽  
Vol 8 (55) ◽  
pp. 94635-94649 ◽  
Author(s):  
Ya-Jun Gui ◽  
Tao Yang ◽  
Qiong Liu ◽  
Cai-Xiu Liao ◽  
Jing-Yuan Chen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Epoxide Hydrolase ◽  
Target Genes ◽  
Soluble Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase Inhibitors

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

2020 ◽  
Vol 23 (5) ◽  
pp. E579-E585
Author(s):  
Xiaojun Zhang ◽  
Caixiu Liao ◽  
Kaijun Sun ◽  
Leiling Liu ◽  
Danyan Xu
Keyword(s):  
Myocardial Infarction ◽  
Protein Expression ◽  
Epoxide Hydrolase ◽  
Target Genes ◽  
Soluble Epoxide Hydrolase ◽  
Distilled Water ◽  
Expression Levels ◽  
Ischemic Region ◽  
Soluble Epoxide Hydrolase Inhibitors ◽  
Potential Therapeutic Application

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.

scholarly journals Soluble Epoxide Hydrolase Inhibitors Regulate Ischemic Arrhythmia by Targeting MicroRNA-1

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanying Chen ◽  
Qiong Liu ◽  
Tian Yang ◽  
Li Shen ◽  
Danyan Xu
Keyword(s):  
Epoxide Hydrolase ◽  
Target Genes ◽  
Serum Response Factor ◽  
Soluble Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase Inhibitors ◽  
Interfering Rna ◽  
Serum Response ◽  
Ischemic Arrhythmia ◽  
Antiarrhythmic Effects

Background: Soluble epoxide hydrolase inhibitors (sEHis) inhibit the degradation of epoxyeicosatrienoic acids (EETs) in cells, and EETs have antiarrhythmic effects. Our previous experiments confirmed that t-AUCB, a preparation of sEHis, inhibited ischemic arrhythmia by negatively regulating microRNA-1 (miR-1), but its specific mechanism remained unclear.Aim: This study aimed to examine the role of serum response factor (SRF) and the PI3K/Akt/GSK3β pathway in t-AUCB-mediated regulation of miR-1 and the interaction between them.Methods/Results: We used SRF small interfering RNA (siSRF), SRF small hairpin (shSRF) RNA sequence adenovirus, PI3K/Akt/GSK3β pathway inhibitors, t-AUCB, and 14,15-EEZE (a preparation of EETs antagonists) to treat mouse cardiomyocytes overexpressing miR-1 and mice with myocardial infarction (MI). We found that silencing SRF attenuated the effects on miR-1 and its target genes KCNJ2 and GJA1 in the presence of t-AUCB, and inhibition of the PI3K/Akt/GSK3β pathway antagonized the effects of t-AUCB on miR-1, KCNJ2, and GJA1, which were associated with PI3Kα, Akt, and Gsk3β but not PI3Kβ or PI3Kγ. Moreover, the PI3K/Akt/GSK3β pathway was involved in the regulation of SRF by t-AUCB, and silencing SRF inhibited the t-AUCB-induced increases in Akt and Gsk3β phosphorylation.Conclusions: Both the SRF and the PI3K/Akt/GSK3β pathway are involved in the t-AUCB-mediated regulation of miR-1, and these factors interact with each other.

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