Mir181 Mediates Tgf-Β-Induced Atrial Endothelial to Mesenchymal Transition and Atrial Subendocardial Fibrosis

Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting, and traditional pharmacological approaches have proved to have important weaknesses. Structural remodeling has been observed in AF paradigms, and is an important feature of the AF substrate, producing fibrosis that alters atrial tissue composition and function. Recently we identified AF was associated with increased atrial subendocardial fibrosis and upregulation of TGF-β in subendocardium. Endothelial to mesenchymal transition (EndoMT), a process involving phenotypic switching from an epithelial to mesenchymal cell, is involved in cardiac fibrosis via TGF-β. Therefore, we hypothesize that TGF-β and AF may contribute to atrial fibrosis via EndMT. In this project, we will test our hypothesis：(I) in vitro use atrial endothelial cell (ECs) primary culture (II) generate transgenic and knock-out mice models, including (1) EndotrackYFP mice, (2) TGFMHC;EndotrackYFP mice, which presents TGF-β-mediated cardial fibrosis and (3) LKB1KOMHC;EndotrackYFP mice , which presents spontaneous AF (III) treat the animal and cells with target miRs, which would be screened by microRNA array as well as statins, which have been suggested antifibrotic in the heart in previous studies. Through this project, we wish to extend our understanding about the molecular mechanism in atrial fibrosis. We hope all of this would advance our knowledge and techniques in understanding AF and reveal a new therapeutic target.

Project ID:PC10608-1481
External Project ID:MOST106-2314-B182-044