Expression of MicroRNA-1,MicroRNA-133,MicroRNA-34a and their Possible Target Protein Ankyrin-B in the Atrium of Patients with Atrial Fibrillation_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHUYun , XIAOYing-bin , FENGZe-zhou , HESi-yi , LIJing-wei ,  CHENGWei

Department of Cardiovascular Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China;

Corresponding author：

CHENGWei, Email: yjchw@126.com

Keywords：

Atrial fibrillation; MicroRNA; Ankyrin-B

DOI：

10.7507/1007-4848.20140070

Video：

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Objective To investigate different expressions of microRNA-1 (microR-1) microRNA-133(microR-133) microRNA-34a (microR-34a) and their possible target protein Ankyrin-B in right atrial appendage of patients with atrial fibrillation (AF) or sinus rhythm (SR) analyze their correlation,and explore novel mechanisms of the pathogenesis and development of AF in microRNA level. Methods Forty right atrial appendage samples of 40 patients with rheumatic heart disease who underwent heart valve replacement in Xinqiao Hospital,Third Military Medical University were included in this study. All the patients were divided into AF group including 8 males and 12 females with their age of 52.9±5.8 years and SR group including 9 males and 11 females with their age of 52.4±6.2 years. The expression of microR-1,microR-133 and microR-34a were examined with RTQ-PCR (real-time quantitative PCR) and calculated with delta delta Ct method. Different expressions of ankyrin-B between AF and SR group were examined with immunohistochemistry and Western Blotting. Results MicroR-1 expression of right atrial appendage of AF group was significantly lower than that of SR group (0.559±0.252 vs. 3.997±1.251,t=-21.455,P=0.000) microR-133 expression of AF group was significantly lower than that of SR group (0.630±0.238 vs. 5.514±1.549,t=24.133,P=0.000) and microR-34a expression of AF group was significantly higher than that of SR group (4.783±2.012 vs. 1.350±0.638,t=12.596,P=0.000). Immunohistochemistry and Western Blotting showed Ankyrin-B expression in right atrial appendage of AF group was significantly lower than that of SR group (0.66±0.45 vs. 1.09±0.42,t=-3.396,P=0.001). Conclusion MicroR-34a may take part in the pathogenesis and development of AF by regulating the expression of Ankyrin-B.

Citation： ZHUYun, XIAOYing-bin, FENGZe-zhou, HESi-yi, LIJing-wei, CHENGWei. Expression of MicroRNA-1,MicroRNA-133,MicroRNA-34a and their Possible Target Protein Ankyrin-B in the Atrium of Patients with Atrial Fibrillation. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2014, 21(2): 244-248. doi: 10.7507/1007-4848.20140070 Copy

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13.	Kim GH.MicroRNA regulation of cardiac conduction and arrhythmias.Transl Res,2013,161 (5):381-392.
14.	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.
15.	Shan H,Zhang Y,Lu Y,et al.Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines.Cardiovasc Res,2009,83 (3):465-472.
16.	Orenes-Piñero E,Montoro-García S,Patel JV,et al.Role of microRNAs in cardiac remodelling:new insights and future perspectives.Int J Cardiol,2013,167 (5):1651-1659.
17.	Belevych AE,Sansom SE,Terentyeva R,et al.MicroRNA-1 and-133 Increase Arrhythmogenesis in Heart Failure by Dissociating Phosphatase Activity from RyR2 Complex.PLoS One,2011,6 (12):e28324.
18.	Vettori S,Gay S,Distler O.Role of MicroRNAs in Fibrosis.Open Rheumatol J,2012,6:130-139.
19.	Hashemi SM,Hund TJ,Mohler PJ.Cardiac ankyrins in health and disease.J Mol Cell Cardiol,2009,47 (2):203-209.
20.	Le Scouarnec S,Bhasin N,Vieyres C,et al.Dysfunction in ankyrin-Bdependent ion channel and transporter targeting causes human sinus node disease.Proc Natl Acad Sci USA,2008,105 (40):15617-15622.
21.	Camors E,Mohler PJ,Bers DM,et al.Ankyrin-B reduction enhances Ca spark-mediated SR Ca release promoting cardiac myocyte arrhythmic activity.J Mol Cell Cardiol,2012,52 (6):1240-1248.
22.	Li J,Kline CF,Hund TJ,et al.Ankyrin-B regulates Kir6.2 membrane expression and function in heart.J Biol Chem,2010,285 (37):28723-28730.
23.	Liu X,Spicarová Z,Rydholm S,et al.Ankyrin B modulates the function of Na,K-ATPase/inositol 1,4,5-trisphosphate receptor signaling microdomain.J Biol Chem,2008,283 (17):11461-11468.
24.	Cunha S,Mohler PJ.Obscurin targets ankyrin-B and protein phosphatase 2A to the cardiac M-line.J Biol Chem,2008,283 (46):3196831980.
25.	Hund TJ,Wright PJ,Dun W,et al.Regulation of the ankyrinB-based targeting pathway following myocardial infarction.Cardiovasc Res,2009,81 (4):742-749.

1. Fuster V,Rydén LE,Cannom DS,et al.ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation:full text a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.Europace,2006,8 (9):651-745.
2. Ezekowitz MD,Aikens TH,Brown A,et al.The evolving field of stroke prevention in patients with atrial fibrillation.Stroke,2010,41 (10 Suppl):S17-S20.
3. 熊健,钟竑,陈苏峰,等.心房颤动中心房重构机制的研究进展.中国胸心血管外科临床杂志,2009,16 (4):283-286.
4. Burstein B,Nattel S.Atrial fibrosis:mechanisms and clinical relevance in atrial fibrillation.J Am Coll Cardiol,2008,51 (8):802-809.
5. Kourliouros A,Savelieva I,Kiotsekoglou A,et al.Current concepts in the pathogenesis of atrial fibrillation.Am Heart J,2009,157 (2):243-252.
6. Xu YM,Sharma D,Li GP,et al.Atrial remodeling:New pathophy siological mechanism of atrial fibrillation.Med Hypotheses,2013,80 (1):53-56.
7. Christ T,Boknik P,Wöhrl S,et al.L-type Ca2⁺ current downregulation in chronic human atrial fibrillation is associated with increased activity of protein phosphatases.Circulation,2004,110 (17):2651-2657.
8. Xiao J,Liang D,Zhang Y,et al.MicroRNA expression signature in atrial fibrillation with mitral stenosis.Physiological Genomics,2011,43 (11):655-664.
9. Sharma D,Li GP,Xu G,et al.Atrial remodeling in atrial fibrillation and some related microRNAs.Cardiology,2011,120 (2):111-121.
10. Boon RA,Iekushi K,Lechner S,et al.MicroRNA-34a regulates cardiac ageing and function.Nature,2013,495 (7439):107-110.
11. Dorn Ⅱ,Gerald W.MicroRNAs in cardiac disease.Transl Res,2011,157 (4):226-235.
12. 段欣,王小华,吉冰洋,等.MicroRNA-1和microRNA-21在缺血预处理、后处理及远端预处理中的表达变化.中国胸心血管外科临床杂志,2012,19 (4):402-407.
13. Kim GH.MicroRNA regulation of cardiac conduction and arrhythmias.Transl Res,2013,161 (5):381-392.
14. 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.
15. Shan H,Zhang Y,Lu Y,et al.Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines.Cardiovasc Res,2009,83 (3):465-472.
16. Orenes-Piñero E,Montoro-García S,Patel JV,et al.Role of microRNAs in cardiac remodelling:new insights and future perspectives.Int J Cardiol,2013,167 (5):1651-1659.
17. Belevych AE,Sansom SE,Terentyeva R,et al.MicroRNA-1 and-133 Increase Arrhythmogenesis in Heart Failure by Dissociating Phosphatase Activity from RyR2 Complex.PLoS One,2011,6 (12):e28324.
18. Vettori S,Gay S,Distler O.Role of MicroRNAs in Fibrosis.Open Rheumatol J,2012,6:130-139.
19. Hashemi SM,Hund TJ,Mohler PJ.Cardiac ankyrins in health and disease.J Mol Cell Cardiol,2009,47 (2):203-209.
20. Le Scouarnec S,Bhasin N,Vieyres C,et al.Dysfunction in ankyrin-Bdependent ion channel and transporter targeting causes human sinus node disease.Proc Natl Acad Sci USA,2008,105 (40):15617-15622.
21. Camors E,Mohler PJ,Bers DM,et al.Ankyrin-B reduction enhances Ca spark-mediated SR Ca release promoting cardiac myocyte arrhythmic activity.J Mol Cell Cardiol,2012,52 (6):1240-1248.
22. Li J,Kline CF,Hund TJ,et al.Ankyrin-B regulates Kir6.2 membrane expression and function in heart.J Biol Chem,2010,285 (37):28723-28730.
23. Liu X,Spicarová Z,Rydholm S,et al.Ankyrin B modulates the function of Na,K-ATPase/inositol 1,4,5-trisphosphate receptor signaling microdomain.J Biol Chem,2008,283 (17):11461-11468.
24. Cunha S,Mohler PJ.Obscurin targets ankyrin-B and protein phosphatase 2A to the cardiac M-line.J Biol Chem,2008,283 (46):3196831980.
25. Hund TJ,Wright PJ,Dun W,et al.Regulation of the ankyrinB-based targeting pathway following myocardial infarction.Cardiovasc Res,2009,81 (4):742-749.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Expression of MicroRNA-1,MicroRNA-133,MicroRNA-34a and their Possible Target Protein Ankyrin-B in the Atrium of Patients with Atrial Fibrillation

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