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MicroRNA miR-133a-3p Facilitates Adrenergic Proarrhythmic Ectopy in Rat Pulmonary Vein Myocardium by Increasing cAMP Content

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Bulletin of Experimental Biology and Medicine Aims and scope

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.

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References

  1. Andrés MD. Therapeutic potential for miR-133a/b to prevent zinc finger homeobox 3 loss of function-dependent atrial fibrillation. Acta Physiol. (Oxf). 2019;227(3):e13372. https://doi.org/10.1111/apha.13372.

    Article  CAS  PubMed  Google Scholar 

  2. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215-233. https://doi.org/10.1016/j.cell.2009.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Belevych AE, Sansom SE, Terentyeva R, Ho HT, Nishijima Y, Martin MM, Jindal HK, Rochira JA, Kunitomo Y, Abdellatif M, Carnes CA, Elton TS, Györke S, Terentyev D. MicroRNA-1 and -133 increase arrhythmogenesis in heart failure by dissociating phosphatase activity from RyR2 complex. PLoS One. 2011;6(12):e28324. https://doi.org/10.1371/journal.pone.0028324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Castaldi A, Zaglia T, Di Mauro V, Carullo P, Viggiani G, Borile G, Di Stefano B, Schiattarella GG, Gualazzi MG, Elia L, Stirparo GG, Colorito ML, Pironti G, Kunderfranco P, Esposito G, Bang ML, Mongillo M, Condorelli G, Catalucci D. MicroRNA-133 modulates the β1-adrenergic receptor transduction cascade. Circ. Res. 2014;115(2):273-283. https://doi.org/10.1161/CIRCRESAHA.115.303252

    Article  CAS  PubMed  Google Scholar 

  5. Condorelli G, Latronico M. V, Cavarretta E. microRNAs in cardiovascular diseases: current knowledge and the road ahead. J. Am. Coll. Cardiol. 2014;63(21):2177-2187. https://doi.org/10.1016/j.jacc.2014.01.050

    Article  CAS  PubMed  Google Scholar 

  6. Deiuliis JA. MicroRNAs as regulators of metabolic disease: pathophysiologic significance and emerging role as biomarkers and therapeutics. Int. J. Obes. (Lond). 2016;40(1):88-101. https://doi.org/10.1038/ijo.2015.170

    Article  CAS  Google Scholar 

  7. D’Souza A, Pearman CM, Wang Y, Nakao S, Logantha SJRJ, Cox C, Bennett H, Zhang Y, Johnsen AB, Linscheid N, Poulsen PC, Elliott J, Coulson J, McPhee J, Robertson A, da Costa Martins PA, Kitmitto A, Wisløff U, Cartwright EJ, Monfredi O, Lundby A, Dobrzynski H, Oceandy D, Morris GM, Boyett MR. Targeting miR-423-5p reverses exercise training-induced HCN4 channel remodeling and sinus bradycardia. Circ. Res. 2017;121(9):1058-1068. https://doi.org/10.1161/CIRCRESAHA.117.311607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Haïssaguerre M, Jaïs P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Métayer P, Clémenty J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N. Engl. J. Med. 1998;339(10):659-666. https://doi.org/10.1056/NEJM199809033391003

    Article  PubMed  Google Scholar 

  9. Karimova VM, Pustovit KB, Abramochkin DV, Kuz’min VS. Effect of purine co-transmitters on automatic activity caused by norepinephrine in myocardial sleeves of pulmonary veins. Bull. Exp. Biol. Med. 2017;162(5):589-593. https://doi.org/10.1007/s10517-017-3664-7

    Article  CAS  PubMed  Google Scholar 

  10. Kuzmin VS, Ivanova AD, Filatova TS, Pustovit KB, Kobylina AA, Atkinson AJ, Petkova M, Voronkov YI, Abramochkin DV, Dobrzynski H. Micro-RNA 133a-3p induces repolarization abnormalities in atrial myocardium and modulates ventricular electrophysiology affecting I Ca,L and Ito currents. Eur. J. Pharmacol. 2021;908:174369. https://doi.org/10.1016/j.ejphar.2021.174369

    Article  CAS  PubMed  Google Scholar 

  11. Kuzmin VS, Ivanova AD, Potekhina VM, Samoilova DV, Ushenin KS, Shvetsova AA, Petrov AM. The susceptibility of the rat pulmonary and caval vein myocardium to the catecholamineinduced ectopy changes oppositely in postnatal development. J. Physiol. 2021;599(11):2803-2821. https://doi.org/10.1113/JP280485

    Article  CAS  PubMed  Google Scholar 

  12. Mikhailov AT, Torrado M. Interplay between cardiac transcription factors and non-coding RNAs in predisposing to atrial fibrillation. J. Mol. Med. (Berl). 2018;96(7):601-610. https://doi.org/10.1007/s00109-018-1647-4

    Article  CAS  PubMed  Google Scholar 

  13. Petkova M, Atkinson AJ, Yanni J, Stuart L, Aminu AJ, Ivanova AD, Pustovit KB, Geragthy C, Feather A, Li N, Zhang Y, Oceandy D, Perde F, Molenaar P, D’Souza A, Fedorov VV, Dobrzynski H. Identification of key small non-coding microRNAs controlling pacemaker mechanisms in the human sinus node. J. Am. Heart Assoc. 2020;9(20):e016590. https://doi.org/10.1161/JAHA.120.016590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tatsuguchi M, Seok HY, Callis TE, Thomson JM, Chen JF, Newman M, Rojas M, Hammond SM, Wang DZ. Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy. J. Mol. Cell. Cardiol. 2007;42(6):1137-1141. https://doi.org/10.1016/j.yjmcc.2007.04.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc. Natl Acad. Sci. USA. 2008;105(35):13027-13032. https://doi.org/10.1073/pnas.0805038105

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to V. S. Kuz’min.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 172, No. 12, pp. 664-668, December, 2021

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Kuz’min, V.S., Kobylina, A.A., Pustovit, K.B. et al. MicroRNA miR-133a-3p Facilitates Adrenergic Proarrhythmic Ectopy in Rat Pulmonary Vein Myocardium by Increasing cAMP Content. Bull Exp Biol Med 172, 671–675 (2022). https://doi.org/10.1007/s10517-022-05454-x

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  • DOI: https://doi.org/10.1007/s10517-022-05454-x

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