Abstract 13638: Endothelial-Mesenchymal Transition in Human Atrial Fibrillation
Background: Atrial fibrosis is a hallmark of atrial structural remodeling leading to persistence of AF. Although fibroblasts are known to play a major role in atrial fibrosis, their source in the adult atrium is unclear. Here we tested the hypothesis that endothelial cells contribute to fibroblasts accumulation through an endothelial-mesenchymal transition (EndMT) in the human atrium during the progression of AF.
Methods and Results: The study group consisted of patients with valvular disease or atrial septal defect who underwent cardiac surgery (n [[Unable to Display Character:  ]]=[[Unable to Display Character:  ]] 38). Atrial tissue was obtained from the left atrial appendage during cardiac surgery. The amount of fibrotic depositions in Masson Trichrome staining of the left atrium (LA) was positively correlated with left atrial dimension (LAD) (y = 0.3004x - 4.395, R2 = 0.3809, P < 0.0001). Also snail and S100A4, indicative of EndMT, in LA quantified by Western blotting showed statistically significant correlations with LAD (y = 0.3728x + 2.793, R2 = 0.1216, P = 0.0319 for SNAIL and y = 0.3728x + 2.793, R2 = 0.1216, P = 0.0319 for S100). The immunofluorescence assay of the LA tissue identified snail and S100A4 expressed within the endocardium which is composed of CD31 positive endothelial cells (Figure). Membrane type 1-matrix metalloproteinase (MT1-MMP) was also expressed within the snail positive endocardium. To provide more evidence that the atrial endothelial cells undergo EndMT during AF progression, we performed immunofluorescence multi-labeling experiments, and identified colocalizations of HSP47, P4HD, ProCL1 with snail and S100A4 within endothelial cells in LA, indicating the mesenchymal phenotype producing collagen.
Conclusions: The present study showed the first evidence that EndMT undergo in the atrium of human AF patients. This observation would help to construct a novel therapeutic approach for the prevention of atrial structural remodeling.
Author Disclosures: T. Kato: None. A. Sekiguchi: None. K. Sagara: None. M. Takamura: None. S. Kaneko: None. T. Aizawa: None. L. Fu: None. T. Yamashita: None.
- © 2014 by American Heart Association, Inc.