TY - JOUR AU - Zhang, Xiaojun AU - Liao, Caixiu AU - Sun, Kaijun AU - Liu, Leiling AU - Xu, Danyan PY - 2020/08/12 Y2 - 2024/03/28 TI - A Soluble Epoxide Hydrolase Inhibitor Upregulated KCNJ12 and KCNIP2 by Downregulating MicroRNA-29 in a Mouse Model of Myocardial Infarction JF - The Heart Surgery Forum JA - HSF VL - 23 IS - 5 SE - DO - 10.1532/hsf.2999 UR - https://journal.hsforum.com/index.php/HSF/article/view/2999 SP - E579-E585 AB - <p class="p1"><span class="s1"><strong>Background:</strong> 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.</span></p><p class="p1"><span class="s2"><strong>Methods:</strong> 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.</span></p><p class="p1"><span class="s1"><strong>Results:</strong> 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.</span></p><p class="p1"><span class="s1"><strong>Conclusion:</strong> 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.</span></p> ER -