open access

Vol 27, No 3 (2020)
Original articles — Basic science and experimental cardiology
Submitted: 2018-05-24
Accepted: 2018-09-28
Published online: 2019-04-11
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MiR-1/133 attenuates cardiomyocyte apoptosis and electrical remodeling in mice with viral myocarditis

Wei Li1, Mengmeng Liu2, Cuifen Zhao2, Cai Chen1, Qingyu Kong2, Zhifeng Cai2, Dong Li3
·
Pubmed: 30994182
·
Cardiol J 2020;27(3):285-294.
Affiliations
  1. Biomedical Engineering Institute, School of Control Science and Engineering, Shandong University, Jinan, China
  2. Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
  3. Research Room of Hypothermia Medicine, Qilu Hospital of Shandong University, Jinan, China

open access

Vol 27, No 3 (2020)
Original articles — Basic science and experimental cardiology
Submitted: 2018-05-24
Accepted: 2018-09-28
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

Page views

2494

Article views/downloads

1250

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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