DNA methylation dysregulations in rheumatic heart valve disease

BMC Cardiovascular Disorders

Research Article

Ran Jing¹  Kangjun Shen²  Xinmin Zhou²  Jiangfeng Yi²  Hui Liu³ 

[1] Department of Cardiology, The Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China;Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, 139. Renmin Road, 410011, Changsha, Hunan, People’s Republic of China;Department of Hemodialysis Center, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China;

关键词: Rheumatic heart valve disease;    DNA methylation;    Dysregulation;   

DOI  :  10.1186/s12872-017-0585-3

 received in 2017-01-02, accepted in 2017-06-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe epigenetic changes underlying the development of rheumatic heart valve disease (RHVD) remain incompletely understood. Limited evidence suggests that abnormal DNA methylation might be involved in the pathogenesis of RHVD. In the present study, we evaluated the DNA methylation dysregulations from myocardial tissue in RHVD patients systematically.MethodsRight atrial myocardial tissue obtained from rheumatic valvular patients who had undergone valve replacements surgery (n = 73) and were compared to healthy controls (n = 4). the promoter methylation level of Intercellular adhesion molecule-1 (ICAM-1) gene and its correlation with ICAM-1 mRNA expression level, the global DNA methylation level and its correlation with age and mRNA expression level of DNA methyltransferase (DNMT) genes were detected.ResultsThe ICAM-1 mRNA expression was increased (healthy control vs. NHYA III, 0.70 ± 0.19 vs. 4.38 ± 3.19, p = 0.011; NYHA IIvs. NHYA III, 2.60 ± 1.99 vs. 4.38 ± 3.19, p = 0.008) and the ICAM-1 gene was hypomethylated in RHVD patients (healthy controls vs. NYHA II, 0.120 ± 0.011 vs. 0.076 ± 0.057, p = 0.039; healthy control vs. NHYA III, 0.120 ± 0.011 vs. 0.041 ± 0.022, p < 0.001; NYHA IIvs. NHYA III, 0.076 ± 0.057 vs. 0.041 ± 0.022, p < 0.001). Meanwhile, The ICAM-1 mRNA expression level has negative correlation with the mean methylation level in the promoter region of ICAM-1 gene (r = −0.459, p < 0.001). The global DNA methylation levels was significantly increased in RHVD patients than in healthy controls (healthy control vs. NHYA III, 0.77 ± 0.28 vs. 2.09 ± 1.20, p = 0.017; NYHA IIvs. NHYA III, 1.57 ± 0.78 vs. 2.09 ± 1.20, p = 0.040) and had positive correlation with age (r = 0.326, p = 0.005), especially for older age group (≥ 60 years). DNMT1 likely plays an essential role in the DNA dysregulations in RHVD patients.ConclusionsOur analysis revealed that DNA methylation dysregulations may be relevant in the pathogenesis of RHVD.

【 授权许可】

CC BY   
© The Author(s). 2017