Atrial tissue expression of receptor for advanced glycation end-products (RAGE) and atrial fibrosis in patients with mitral valve disease

Abstract

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.

Keywords: Atrial fibrillation; Atrial fibrosis; Mitral valve disease; RAGE.