Key result
The sEHi t-AUCB dose-dependently prevented MI-induced increases in miR-29 and decreases in KCNJ12 and KCNIP2 expression in a mouse model of myocardial infarction.
Why the study?
The mechanisms underlying the anti-arrhythmic effects of the soluble epoxide hydrolase inhibitor t-AUCB after myocardial infarction, including whether it modulates miR-29 and its target genes KCNJ12 and KCNIP2, were unknown.
Does the sEHi t-AUCB modulate miR-29 and its target genes KCNJ12 and KCNIP2 in a mouse model of myocardial infarction?
Does the sEHi t-AUCB modulate miR-29 and its target genes KCNJ12 and KCNIP2 in a mouse model of myocardial infarction?
The sEHi t-AUCB regulates miR-29 and its target genes KCNJ12 and KCNIP2, providing a potential mechanistic basis for its anti-arrhythmic effects after myocardial infarction.
Hypothesis-generating for sEHi anti-arrhythmic effects post-MI; human studies needed before clinical relevance.
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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Zhang et al. (2020) studied Myocardial Infarction. t-AUCB vs. distilled water only was evaluated on miR-29, KCNJ12, and KCNIP2 expression levels. The sEHi t-AUCB dose-dependently prevented MI-induced increases in miR-29 and decreases in KCNJ12 and KCNIP2 expression in a mouse model of myocardial infarction.
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