open access

Vol 27, No 3 (2020)
Original articles — Basic science and experimental cardiology
Published online: 2019-04-11
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MiR-1/133 attenuates cardiomyocyte apoptosis and electrical remodeling in mice with viral myocarditis

Wei Li, Mengmeng Liu, Cuifen Zhao, Cai Chen, Qingyu Kong, Zhifeng Cai, Dong Li
DOI: 10.5603/CJ.a2019.0036
·
Pubmed: 30994182
·
Cardiol J 2020;27(3):285-294.

open access

Vol 27, No 3 (2020)
Original articles — Basic science and experimental cardiology
Published online: 2019-04-11

Abstract

Background: The role of miR-1 and miR-133 in regulating the expression of potassium and calcium ion channels, and mediating cardiomyocyte apoptosis in mice with viral myocarditis (VMC) is investigated herein.

Methods: Male Balb/c mice were randomly divided into groups: control group, VMC group, VMC + miR-1/133 mimics group, or VMC + miR-1/133 negative control (NC) group. VMC was induced with coxsackievirus B3 (CVB3). MiR-1/133 mimics ameliorated cardiac dysfunction in VMC mice and was compared to the VMC+NC group.

Results: Hematoxylin and eosin staining showed a well-arranged myocardium without inflammatory cell infiltration in the myocardial matrix of the control group. However, in the VMC and VMC+NC groups, the myocardium was disorganized and swollen with necrosis, and the myocardial matrix was infiltrated with inflammatory cells. These changes were alleviated by miR-1/133 mimics. TUNEL staining revealed decreased cardiomyocyte apoptosis in the VMC + miR-1/133 mimics group compared with the VMC group. In addition, miR-1/133 mimics up-regulated the expression of miR-1 and miR-133, the potassium channel genes Kcnd2 and Kcnj2, as well as Bcl-2, and down-regulated the expression of the potassium channel suppressor gene Irx5, L-type calcium channel subunit gene a1c (Cacna1c), Bax, and caspase-9 in the myocardium of VMC mice. MiR-1/133 also up-regulated the protein levels of Kv4.2 and Kir2.1, and down-regulated the expression of CaV1.2 in the myocardium of VMC mice.

Conclusions: MiR-1 and miR-133 decreased cardiomyocyte apoptosis by mediating the expression of apoptosis-related genes in the hearts of VMC mice.

Abstract

Background: The role of miR-1 and miR-133 in regulating the expression of potassium and calcium ion channels, and mediating cardiomyocyte apoptosis in mice with viral myocarditis (VMC) is investigated herein.

Methods: Male Balb/c mice were randomly divided into groups: control group, VMC group, VMC + miR-1/133 mimics group, or VMC + miR-1/133 negative control (NC) group. VMC was induced with coxsackievirus B3 (CVB3). MiR-1/133 mimics ameliorated cardiac dysfunction in VMC mice and was compared to the VMC+NC group.

Results: Hematoxylin and eosin staining showed a well-arranged myocardium without inflammatory cell infiltration in the myocardial matrix of the control group. However, in the VMC and VMC+NC groups, the myocardium was disorganized and swollen with necrosis, and the myocardial matrix was infiltrated with inflammatory cells. These changes were alleviated by miR-1/133 mimics. TUNEL staining revealed decreased cardiomyocyte apoptosis in the VMC + miR-1/133 mimics group compared with the VMC group. In addition, miR-1/133 mimics up-regulated the expression of miR-1 and miR-133, the potassium channel genes Kcnd2 and Kcnj2, as well as Bcl-2, and down-regulated the expression of the potassium channel suppressor gene Irx5, L-type calcium channel subunit gene a1c (Cacna1c), Bax, and caspase-9 in the myocardium of VMC mice. MiR-1/133 also up-regulated the protein levels of Kv4.2 and Kir2.1, and down-regulated the expression of CaV1.2 in the myocardium of VMC mice.

Conclusions: MiR-1 and miR-133 decreased cardiomyocyte apoptosis by mediating the expression of apoptosis-related genes in the hearts of VMC mice.

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Keywords

miR-1, miR-133, viral myocarditis, ion channels, cell apoptosis infarction, coronary, psoriasis, anaphylaxis

About this article
Title

MiR-1/133 attenuates cardiomyocyte apoptosis and electrical remodeling in mice with viral myocarditis

Journal

Cardiology Journal

Issue

Vol 27, No 3 (2020)

Pages

285-294

Published online

2019-04-11

DOI

10.5603/CJ.a2019.0036

Pubmed

30994182

Bibliographic record

Cardiol J 2020;27(3):285-294.

Keywords

miR-1
miR-133
viral myocarditis
ion channels
cell apoptosis infarction
coronary
psoriasis
anaphylaxis

Authors

Wei Li
Mengmeng Liu
Cuifen Zhao
Cai Chen
Qingyu Kong
Zhifeng Cai
Dong Li

References (35)
  1. Lagos-Quintana M, Rauhut R, Yalcin A, et al. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002; 12(9): 735–739.
  2. Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature. 2005; 436(7048): 214–220.
  3. Yang B, Lin H, Xiao J, et al. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med. 2007; 13(4): 486–491.
  4. Li YD, Hong YF, Yusufuaji Y, et al. Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation. Mol Med Rep. 2015; 12(3): 3243–3248.
  5. Girmatsion Z, Biliczki P, Bonauer A, et al. Changes in microRNA-1 expression and IK1 up-regulation in human atrial fibrillation. Heart Rhythm. 2009; 6(12): 1802–1809.
  6. da Costa Martins PA, Bourajjaj M, Gladka M, et al. Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling. Circulation. 2008; 118(15): 1567–1576.
  7. Lu Y, Xiao J, Lin H, et al. A single anti-microRNA antisense oligodeoxyribonucleotide (AMO) targeting multiple microRNAs offers an improved approach for microRNA interference. Nucleic Acids Res. 2009; 37(3): e24.
  8. Feldman A, McNamara D. Myocarditis. N Engl J Med. 2000; 343(19): 1388–1398.
  9. Xu F, Liu G, Liu Q, et al. RNA interference of influenza A virus replication by microRNA-adapted lentiviral loop short hairpin RNA. J Gen Virol. 2015; 96(10): 2971–2981.
  10. Myers R, Timofeyev V, Li N, et al. Feedback mechanisms for cardiac-specific microRNAs and cAMP signaling in electrical remodeling. Circ Arrhythm Electrophysiol. 2015; 8(4): 942–950.
  11. Kinali M, Arechavala-Gomeza V, Cirak S, et al. Muscle histology vs MRI in Duchenne muscular dystrophy. Neurology. 2011; 76(4): 346–353.
  12. Liu Z, Carthy CM, Cheung P, et al. Structural and functional analysis of the 5' untranslated region of coxsackievirus B3 RNA: In vivo translational and infectivity studies of full-length mutants. Virology. 1999; 265(2): 206–217.
  13. Li Lm. Comparison of plasma microRNA-1 and cardiac troponin T in early diagnosis of patients with acute myocardial infarction. World Journal of Emergency Medicine. 2014; 5(3): 182–186.
  14. Cheng Y, Ji R, Yue J, et al. MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy? Am J Pathol. 2007; 170(6): 1831–1840.
  15. Busk PK, Cirera S. MicroRNA profiling in early hypertrophic growth of the left ventricle in rats. Biochem Biophys Res Commun. 2010; 396(4): 989–993.
  16. Carè A, Catalucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med. 2007; 13(5): 613–618.
  17. Liang Yu, Ridzon D, Wong L, et al. Characterization of microRNA expression profiles in normal human tissues. BMC Genomics. 2007; 8: 166.
  18. Luo X, Zhang H, Xiao J, et al. Regulation of human cardiac ion channel genes by microRNAs: theoretical perspective and pathophysiological implications. Cell Physiol Biochem. 2010; 25(6): 571–586.
  19. Lin CC, Chang YM, Pan CT, et al. Functional evolution of cardiac microRNAs in heart development and functions. Mol Biol Evol. 2014; 31(10): 2722–2734.
  20. Sayed D, Hong C, Chen IY, et al. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res. 2007; 100(3): 416–424.
  21. Diniz GP, Lino CA, Guedes EC, et al. Cardiac microRNA-133 is down-regulated in thyroid hormone-mediated cardiac hypertrophy partially via Type 1 Angiotensin II receptor. Basic Res Cardiol. 2015; 110(5): 49.
  22. Hedley PL, Carlsen AL, Christiansen KM, et al. MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome. Scand J Clin Lab Invest. 2014; 74(6): 485–491.
  23. Wang GK, Zhu JQ, Zhang JT, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J. 2010; 31(6): 659–666.
  24. Woodruff JF. Viral myocarditis. A review. Am J Pathol. 1980; 101(2): 425–484.
  25. Reyes MP, Lerner AM. Coxsackievirus myocarditis--with special reference to acute and chronic effects. Prog Cardiovasc Dis. 1985; 27(6): 373–394.
  26. Kishimoto C, Misaki T, Crumpacker CS, et al. Serial immunologic identification of lymphocyte subsets in murine coxsackievirus B3 myocarditis: different kinetics and significance of lymphocyte subsets in the heart and in peripheral blood. Circulation. 1988; 77(3): 645–653.
  27. Xu C, Lu Y, Pan Z, et al. The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. J Cell Sci. 2007; 120(Pt 17): 3045–3052.
  28. Zhang L, Dong Y, Zhu N, et al. microRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer. Mol Cancer. 2014; 13: 124.
  29. Besser J, Malan D, Wystub K, et al. MiRNA-1/133a clusters regulate adrenergic control of cardiac repolarization. PLoS One. 2014; 9(11): e113449.
  30. Costantini DL, Arruda EP, Agarwal P, et al. The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. Cell. 2005; 123(2): 347–358.
  31. Gómez R, Caballero R, Barana A, et al. Structural basis of drugs that increase cardiac inward rectifier Kir2.1 currents. Cardiovasc Res. 2014; 104(2): 337–346.
  32. Wang Lu, Yuan Ye, Li J, et al. MicroRNA-1 aggravates cardiac oxidative stress by post-transcriptional modification of the antioxidant network. Cell Stress Chaperones. 2015; 20(3): 411–420.
  33. Lu Y, Zhang Y, Shan H, et al. MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction: a new mechanism for ischaemic cardioprotection. Cardiovasc Res. 2009; 84(3): 434–441.
  34. Diaz RJ, Zobel C, Cho HC, et al. Selective inhibition of inward rectifier K+ channels (Kir2.1 or Kir2.2) abolishes protection by ischemic preconditioning in rabbit ventricular cardiomyocytes. Circ Res. 2004; 95(3): 325–332.
  35. Zhao Y, Ransom JF, Li A, et al. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell. 2007; 129(2): 303–317.

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