title: Endothelial-mesenchymal transition in human atrial fibrillation.
abstract: Atrial fibrosis is a hallmark of atrial structural remodeling leading to the persistence of atrial fibrillation. Although fibroblasts play a major role in atrial fibrosis, their source in the adult atrium is unclear. We tested the hypothesis that endothelial cells contribute to fibroblast accumulation through an endothelial-mesenchymal transition in the atrium of patients with atrial fibrillation.
  
  
  
  The study group consisted of patients with atrial fibrillation and valvular disease or atrial septal defect who underwent left atrial appendectomy during cardiac surgery (n=38). The amount of fibrotic depositions in the left atrium positively correlated with left atrial dimension. Furthermore, snail and S100A4, indicative of endothelial-mesenchymal transition, were quantified in the left atrium using western blot analysis, which showed statistically significant correlations with left atrial dimension. Immunofluorescence assay of the left atrial tissue identified snail and S100A4 being expressed within the endocardium which is composed of CD31+cells. The snail-positive endocardium also showed the expression of membrane type 1-matrix metalloproteinase. Immunofluorescence multi-labeling experiments identified that heat shock protein 47, prolyl-4-hydroxylase, and procollagen type 1 co-localized with snail and S100A4 within the endothelial cells of the left atrium, indicating the mesenchymal phenotype to produce collagen.
  
  
  
  In this study, we showed that the endothelial-mesenchymal transition occurs in the atrium of patients with atrial fibrillation. This observation should help in constructing a novel therapeutic approach for preventing atrial structural remodeling.
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; The Cardiovascular Institute, Tokyo, Japan. Electronic address: takeshikato@me.com.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sekiguchi
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sagara
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanabe
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takamura
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Tadanori
authors.initials: T
authors.lastname: Aizawa
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Long-Tai
authors.initials: LT
authors.lastname: Fu
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000503:physiopathology*; D064752:Atrial Remodeling / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism; D004699:Endocardium / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D008875:Middle Aged; D064828:Prolyl Hydroxylases / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4 / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D050958:HSP47 Heat-Shock Proteins; D000071999:S100 Calcium-Binding Protein A4; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C077591:S100A4 protein, human; D064828:Prolyl Hydroxylases; D053511:Matrix Metalloproteinase 14
keywords: Atrial fibrillation; Endothelial–mesenchymal transition; Fibroblast; Fibrosis; Remodeling