Epicardial and endothelial cell activation concurs with extracellular matrix remodeling in atrial fibrillation

Abstract Background Improved understanding of the interconnectedness of structural remodeling processes in atrial fibrillation (AF) in patients could identify targets for future therapies. Methods We present transcriptome sequencing of atrial tissues of patients without AF, with paroxysmal AF, and p...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Nicoline W. E. van den Berg, Makiri Kawasaki, Benedetta Fabrizi, Fransisca A. Nariswari, Arianne C. Verduijn, Jolien Neefs, Robin Wesselink, Rushd F. M. Al‐Shama, Allard C. van der Wal, Onno J. de Boer, Jan Aten, Antoine H. G. Driessen, Aldo Jongejan, Joris R. de Groot
Formato: article
Lenguaje:EN
Publicado: Wiley 2021
Materias:
Acceso en línea:https://doaj.org/article/1856597343d24eb6845f5da16fe68c38
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:Abstract Background Improved understanding of the interconnectedness of structural remodeling processes in atrial fibrillation (AF) in patients could identify targets for future therapies. Methods We present transcriptome sequencing of atrial tissues of patients without AF, with paroxysmal AF, and persistent AF (total n = 64). RNA expression levels were validated in the same and an independent cohort with qPCR. Biological processes were assessed with histological and immunohistochemical analyses. Results In AF patients, epicardial cell gene expression decreased, contrasting with an upregulation of epithelial‐to‐mesenchymal transition (EMT) and mesenchymal cell gene expression. Immunohistochemistry demonstrated thickening of the epicardium and an increased proportion of (myo)fibroblast‐like cells in the myocardium, supporting enhanced EMT in AF. We furthermore report an upregulation of endothelial cell proliferation, angiogenesis, and endothelial signaling. EMT and endothelial cell proliferation concurred with increased interstitial (myo)fibroblast‐like cells and extracellular matrix gene expression including enhanced tenascin‐C, thrombospondins, biglycan, and versican. Morphological analyses discovered increased and redistributed glycosaminoglycans and collagens in the atria of AF patients. Signaling pathways, including cell–matrix interactions, PI3K‐AKT, and Notch signaling that could regulate mesenchymal cell activation, were upregulated. Conclusion Our results suggest that EMT and endothelial cell proliferation work in concert and characterize the (myo)fibroblast recruitment and ECM remodeling of AF. These processes could guide future research toward the discovery of targets for AF therapy.