Department of Human and Animal Physiology, Faculty of Biology, M. V. Lomonosov Moscow State University, Moscow, Russia.
Scientific Research Laboratory of Electrophysiology, Pirogov Russian National Research Medical University, Ministry of the Health of the Russian Federation, Moscow, Russia.
Bull Exp Biol Med. 2022 Apr;172(6):671-675. doi: 10.1007/s10517-022-05454-x. Epub 2022 May 2.
Cardiac-specific microRNA miR-133a-3p modulates adrenergic signaling. Adrenergic receptors and their intracellular pathways are the key players in proarrhythmic ectopy derived from the myocardial sleeves of the pulmonary veins. We studied the effect of miR-133a-3p on ectopy induced by norepinephrine in myocardial tissue of rat pulmonary veins. Using microelectrode technique, we revealed facilitation of proarrhythmic pattern of spontaneous bursts of action potentials induced by norepinephrine in tissue preparations of the pulmonary veins isolated from rats in 24 h after injection of a transfection mixture containing miR-133a-3p (1 mg/kg) in vivo. According to ELISA data, the cAMP level in the pulmonary vein myocardium of rats receiving miR-133a-3p was 2-fold higher than in control animals. Bioinformatic analysis showed that mRNA of protein phosphatases and some phosphodiesterases are most probable targets of miR-133a-3p. The proarrhythmic effect of miR-133a-3p can be related to inhibition of the expression of phosphodiesterases accompanied by cAMP accumulation and increased intracellular β-adrenergic signaling.
心脏特异性 microRNA miR-133a-3p 调节肾上腺素能信号。肾上腺素能受体及其细胞内途径是源自肺静脉心肌袖的致心律失常性异位的关键因素。我们研究了 miR-133a-3p 对去甲肾上腺素诱导的大鼠肺静脉心肌组织异位的影响。使用微电极技术，我们揭示了在体内注射含有 miR-133a-3p（1mg/kg）的转染混合物 24 小时后分离的大鼠肺静脉组织中，去甲肾上腺素诱导的动作电位自发性爆发的致心律失常模式得到促进。根据 ELISA 数据，接受 miR-133a-3p 的大鼠肺静脉心肌中的 cAMP 水平比对照动物高 2 倍。生物信息学分析表明，蛋白磷酸酶和一些磷酸二酯酶的 mRNA 是 miR-133a-3p 的最可能靶标。miR-133a-3p 的致心律失常作用可能与抑制磷酸二酯酶的表达有关，同时伴随着 cAMP 积累和细胞内β肾上腺素能信号的增强。
