Abstract
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.
Highlights
The epigenetic changes underlying the development of rheumatic heart valve disease (RHVD) remain incompletely understood
The mRNA expression level and the promoter methylation pattern of Intercellular adhesion molecule-1 (ICAM-1) gene Compared with healthy controls and New York heart association (NYHA) II patients, the mRNA levels were significantly increased in NHYA III patients
The mean methylation levels were significantly decreased with the progression of RHVD
Summary
The 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. The progression of valve damage eventually leads to congestive heart failure [1]. In most developing countries, such as China, RHVD remains the main cause of heart valve disease. The pathogenesis of RHVD is complex and still remains incompletely understood. Inflammation and auto-immune response were all involved in the pathogenesis [3, 4]. Increasing evidences had been showed that DNA methylation dysregulation plays an important role in the occurrence and development of complex diseases in recent years. Most DNA methylation deregulation studies have focused on cancer and auto-immune disease [13, 14]. The impact of DNA methylation upon the initiation/progression of cardiovascular diseases has not been investigated in detail [15]
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