DNA Methylation Dysregulations in Valvular Atrial Fibrillation

Overview

Journal Clin Cardiol

Specialty Cardiology & Vascular Diseases

Date 2017 Aug 29

PMID 28846808

Citations 13

Authors

Kangjun Shen

Tao Tu

Zhaoshun Yuan

Jiangfeng Yi

Yangzhao Zhou

Xiaobo Liao

Qiming Liu

Xinmin Zhou

Affiliations

Soon will be listed here.

Abstract

Background: The epigenetic changes underlying the development of atrial fibrillation (AF) remain incompletely understood. Limited evidence suggests that abnormal DNA methylation might be involved in the pathogenesis of AF. In the present study, we evaluated the methylation status of genomic DNA from myocardial tissue in AF patients and sinus rhythm (SR) patients systematically.

Hypothesis: DNA methylation dysregulations will be associated with valvular AF.

Methods: Right atrial myocardial tissue was obtained from rheumatic valvular patients who had undergone valve replacement surgery (SR group, n = 10; AF group, n = 10). The global DNA methylation level, the promoter methylation level of the natriuretic peptide receptor-A gene (NPRA), and its correlation with the mRNA expression level of DNA methyltransferase genes were detected.

Results: The global DNA methylation level was significantly higher in the AF group than in the SR group (P < 0.05). The NPRA mRNA expression was decreased and the NPRA gene was hypermethylated in the AF group (P < 0.05). Meanwhile, the NPRA mRNA expression level has a negative correlation with the mean methylation level in the promoter region of the NPRA gene.

Conclusions: DNA methylation dysregulations may be relevant in the pathogenesis of AF. DNA methyltransferase 3B likely plays an essential role in the DNA methylation dysregulations in AF.

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References

Zeng Q, Wei M, Zhang W, Zhang Y, Zhong J . Level Of Natriuretic Peptide Determines Outcome In Atrial Fibrillation. J Atr Fibrillation. 2017; 2(4):227. PMC: 4956203. DOI: 10.4022/jafib.227. View

Zhong J, Agha G, Baccarelli A . The Role of DNA Methylation in Cardiovascular Risk and Disease: Methodological Aspects, Study Design, and Data Analysis for Epidemiological Studies. Circ Res. 2016; 118(1):119-131. PMC: 4743554. DOI: 10.1161/CIRCRESAHA.115.305206. View

Kao Y, Chen Y, Chung C, Lien G, Chen S, Kuo C . Heart failure and angiotensin II modulate atrial Pitx2c promotor methylation. Clin Exp Pharmacol Physiol. 2013; 40(6):379-84. DOI: 10.1111/1440-1681.12089. View

Wang B, Yin B, He B, Chen C, Zhao M, Zhang W . Overexpression of DNA damage-induced 45 α gene contributes to esophageal squamous cell cancer by promoter hypomethylation. J Exp Clin Cancer Res. 2012; 31:11. PMC: 3364148. DOI: 10.1186/1756-9966-31-11. View

Koutsis G, Siasos G, Spengos K . The emerging role of microRNA in stroke. Curr Top Med Chem. 2013; 13(13):1573-88. DOI: 10.2174/15680266113139990106. View

Pogribny I, Beland F . DNA hypomethylation in the origin and pathogenesis of human diseases. Cell Mol Life Sci. 2009; 66(14):2249-61. PMC: 11115809. DOI: 10.1007/s00018-009-0015-5. View

Li J, He Y, Ke H, Jin Y, Jiang Z, Zhong G . Plasma oxidative stress and inflammatory biomarkers are associated with the sizes of the left atrium and pulmonary vein in atrial fibrillation patients. Clin Cardiol. 2017; 40(2):89-94. PMC: 6490400. DOI: 10.1002/clc.22633. View

Long C, Yin B, Lu Q, Zhou X, Hu J, Yang Y . Promoter hypermethylation of the RUNX3 gene in esophageal squamous cell carcinoma. Cancer Invest. 2007; 25(8):685-90. DOI: 10.1080/07357900701561131. View

Kurosaki K, Tada H, Hashimoto T, Ito S, Miyaji K, Naito S . Plasma natriuretic peptide concentrations as a predictor for successful catheter ablation in patients with drug-refractory atrial fibrillation. Circ J. 2007; 71(3):313-20. DOI: 10.1253/circj.71.313. View

10.

Sharma P, Kumar J, Garg G, Kumar A, Patowary A, Karthikeyan G . Detection of altered global DNA methylation in coronary artery disease patients. DNA Cell Biol. 2008; 27(7):357-65. DOI: 10.1089/dna.2007.0694. View

11.

Muka T, Koromani F, Portilla E, OConnor A, Bramer W, Troup J . The role of epigenetic modifications in cardiovascular disease: A systematic review. Int J Cardiol. 2016; 212:174-83. DOI: 10.1016/j.ijcard.2016.03.062. View

12.

Potter L, Yoder A, Flora D, Antos L, Dickey D . Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handb Exp Pharmacol. 2008; (191):341-66. PMC: 4855512. DOI: 10.1007/978-3-540-68964-5_15. View

13.

Chen C, Yin B, Wei Q, Li D, Hu J, Yu F . Aberrant DNA methylation in thymic epithelial tumors. Cancer Invest. 2009; 27(5):582-91. DOI: 10.1080/07357900802620869. View

14.

Whayne T . Epigenetics in the development, modification, and prevention of cardiovascular disease. Mol Biol Rep. 2014; 42(4):765-76. DOI: 10.1007/s11033-014-3727-z. View

15.

Heijman J, Voigt N, Nattel S, Dobrev D . Cellular and molecular electrophysiology of atrial fibrillation initiation, maintenance, and progression. Circ Res. 2014; 114(9):1483-99. DOI: 10.1161/CIRCRESAHA.114.302226. View

16.

Andrade J, Khairy P, Dobrev D, Nattel S . The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circ Res. 2014; 114(9):1453-68. DOI: 10.1161/CIRCRESAHA.114.303211. View

17.

Shen K, Tu T, Yuan Z, Yi J, Zhou Y, Liao X . DNA methylation dysregulations in valvular atrial fibrillation. Clin Cardiol. 2017; 40(9):686-691. PMC: 6490353. DOI: 10.1002/clc.22715. View

18.

Pandey K . Guanylyl cyclase / atrial natriuretic peptide receptor-A: role in the pathophysiology of cardiovascular regulation. Can J Physiol Pharmacol. 2011; 89(8):557-73. PMC: 3345283. DOI: 10.1139/y11-054. View

19.

Choi S, Ryu Y, Kee H, Cho S, Kim G, Cho J . Tubastatin A suppresses renal fibrosis via regulation of epigenetic histone modification and Smad3-dependent fibrotic genes. Vascul Pharmacol. 2015; 72:130-40. DOI: 10.1016/j.vph.2015.04.006. View

20.

Kim S, Morales C, Gillette T, Hill J . Epigenetic regulation in heart failure. Curr Opin Cardiol. 2016; 31(3):255-65. PMC: 4955576. DOI: 10.1097/HCO.0000000000000276. View