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MicroRNA miR-133a-3p Facilitates Adrenergic Proarrhythmic Ectopy in Rat Pulmonary Vein Myocardium by Increasing cAMP
V S Kuz'min1,2, A A Kobylina3, K B Pustovit3
1Department of Human and Animal Physiology, Faculty of Biology, M. V. Lomonosov Moscow State University, Moscow, Russia. ku290381@mail.ru.
Abstract:
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.
Insights
MicroRNA miR-133a-3p can worsen heart arrhythmias. This microRNA increases cyclic adenosine monophosphate (cAMP) levels, enhancing beta-adrenergic signaling and promoting abnormal heartbeats in pulmonary veins.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cardiac Electrophysiology
Background:
- Adrenergic signaling pathways are critical in cardiac arrhythmias, particularly ectopy originating from pulmonary vein myocardial sleeves.
- MicroRNAs (miRNAs) are key regulators of gene expression with significant roles in cardiovascular function.
Purpose of the Study:
- To investigate the effect of cardiac-specific microRNA miR-133a-3p on norepinephrine-induced cardiac ectopy in rat pulmonary vein myocardial tissue.
- To elucidate the molecular mechanisms underlying miR-133a-3p's influence on adrenergic signaling and arrhythmogenesis.
Main Methods:
- In vivo transfection of rats with miR-133a-3p followed by ex vivo assessment of pulmonary vein tissue.
- Microelectrode recordings to analyze action potential patterns and spontaneous bursts.
- Enzyme-linked immunosorbent assay (ELISA) to quantify cyclic adenosine monophosphate (cAMP) levels.
- Bioinformatic analysis to predict miR-133a-3p targets.
Main Results:
- miR-133a-3p transfection facilitated proarrhythmic spontaneous action potential bursts induced by norepinephrine.
- cAMP levels in the pulmonary vein myocardium were significantly elevated (2-fold) in miR-133a-3p treated rats compared to controls.
- Bioinformatic analysis identified protein phosphatases and phosphodiesterases as likely targets of miR-133a-3p.
Conclusions:
- miR-133a-3p promotes proarrhythmic effects in pulmonary vein myocardium.
- The proarrhythmic action of miR-133a-3p is associated with increased cAMP levels and enhanced intracellular beta-adrenergic signaling, potentially via phosphodiesterase inhibition.
