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Background: MicroRNAs (miRs) regulate gene expression in heart failure. Circulating miRs as biomarkers for heart failure in mitral regurgitation patients (MR) remain unexplored., Methods: This case-control study enrolled 32 MR patients with heart failure, 16 asymptomatic MR patients, and 12 control subjects without heart failure. We used next generation sequencing to study the gene expression profiles in the sera, and quantitative RT-PCR to study serum and tissue miRs in the left atria., Results: Next generation sequencing analysis and enrichment analysis showed that 25 miRs were differentially expressed in the sera of MR patients with heart failure compared to control subjects. The circulating miR-148b-3p (p=0.002) and miR-409-3p (p=0.010) were significantly down-regulated in the MR patients with heart failure compared to control subjects. However, only circulation miR-148b-3p was significantly down-regulated in the MR patients without heart failure compared to control subjects (p=0.009). The tissue miR-409-3p was significantly down-regulated in the MR patients with heart failure compared to 3 purchased normal controls (p=0.041). Notably, the tissue RASGRP3 mRNA, target gene of miR-409-3p, was significantly up-regulated in the MR patients with heart failure compared to normal controls (p=0.010). The tissue FRY (p=0.010) and GADD45A (p=0.010) mRNAs, target genes of miR-148b-3p, were significantly up-regulated in the MR patients with heart failure compared to normal controls., Conclusions: Circulating miR-148b-3p might serve as biomarker for future development of heart failure and miR-409-3p might serve as biomarker for incident heart failure in MR patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: It has been reported that receptor for advanced glycation end-products (RAGE) plays a significant role in cardiac fibrosis. Nonetheless, the precise relationship between the RAGE and atrial fibrosis has never been studied in humans. The aim of this study was to determine whether degree of atrial fibrosis was associated with atrial tissue expression of RAGE in patients with mitral valve disease (MVD)., Methods: We collected human left atrial (LA) appendage tissue from 25 patients who underwent mitral valve surgery. We quantified the expression of RAGE and other protein markers by Western blotting and compared these levels with histological evaluations., Results: RAGE expression in the LA appendage tissue was significantly correlated with atrial fibrosis (r=0.681, p=0.001). RAGE expression (regression coefficient [B] 9.49, 95% confidence interval [CI] 4.76-14.2, p<0.001) and LA diameter (B 0.43, 95% CI 0.13-0.74, p=0.008) were independently associated with degree of atrial fibrosis in multiple linear regression analysis. RAGE expression was significantly correlated with protein expression of von Willebrand factor (r=0.659, p<0.001), vascular endothelial cadherin (r=0.757, p<0.001), ICAM-1 (r=0.568, p=0.003), and PECAM-1 (r=0.423, p=0.035) in the LA appendage tissue. In addition, patients with severe mitral stenosis (MS) had higher atrial RAGE expression than those with no, mild, or moderate MS (p=0.013). Patients with MVD and atrial fibrillation (AF) had more severe atrial fibrosis (p=0.024) and higher RAGE expression (p=0.047) than those who remained in sinus rhythm., Conclusions: Atrial tissue expression of RAGE was significantly associated with atrial fibrosis, severe MS, and AF rhythm in patients with MVD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Until today, FBN1 gene mutation characteristics were not compared with clinical features for the prediction of mitral valve disease progression., Methods: Therefore, we conducted a study of 116 patients (53 men, 63 women aged 33 ± 15 years) with a causative FBN1 gene mutation and ≤ moderate mitral valve regurgitation at baseline., Results: During 7.4 ± 6.8 years 30 patients developed progression of mitral valve regurgitation ≥ 1 grade (primary endpoint), and 26 patients required mitral valve surgery (secondary endpoint). Cox regression analysis identified an association of atrial fibrillation (hazard ratio (HR)=2.703; 95% confidence interval (CI) 1.013-7.211; P=.047), left ventricular ejection fraction (HR=.970; 95%CI .944-.997; P=.032), indexed end-diastolic left ventricular diameter (HR=15.165; 95%CI 4.498-51.128; P<.001), indexed left atrial diameter (HR=1.107; 95%CI 1.045-1.173; P=.001), tricuspid valve prolapse (HR=2.599; 95%CI 1.243-5.437; P=.011), posterior leaflet prolapse (HR=1.075; 95%CI 1.023-1.130; P=.009), and posterior leaflet thickening (HR=3.368; 95%CI 1.265-8.968; P=.015) with progression of mitral valve disease, whereas none of the FBN1 gene mutation characteristics were associated with progression of mitral valve disease. However, Cox regression analysis identified a marginal relationship of FBN1 gene mutations located both in a transforming-growth-factor beta-binding protein-like (TGFb-BP) domain (HR=3.453; 95%CI .982-12.143; P=.053), and in the calcium-binding epidermal growth factor-like (cbEGF) domain (HR=2.909; 95%CI .957-8.848; P=.060) with mitral valve surgery, a finding that was corroborated by Kaplan-Meier analysis (P=.014; and P=.041, respectively)., Conclusion: Clinical features were better predictors of mitral valve disease progression than FBN1 gene mutation characteristics., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)