Tgf-Β Contributes to Atrial Fibrosis via Endothelial to Mesenchymal Transition

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 it was showed 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. Recently, we have harvested atrial ECs from rat and found TGF-β contributes to EndMT in atrial ECs. Meanwhile, CD44 is effective in reducing TGF-β-induced EndMT. In this project, we will (1) generate and characterize atrial endothelial cell (ECs) primary culture (2) investigate if atrial ECs contribute to atrial fibrosis via EndoMT. (3) generatie TGFMHC;EndotrackYFP mice (4) generate of cardiac-specific LKB1(liver kinase B1) knockout mice, which is characterized with spontaneous AF (5) generatie TGFMHC;EC-specific CD44 KO mice. Through this project, the characteristics of atrial ECs with be revealed. Its participation and potential underlying molecular mechanism in atrial fibrosis will be approached by biochemistry and stringent animal study. We hope all of this would advance our knowledge and techniques in understanding AF and reveal a new therapeutic target.

Project ID:PC10507-0205
External Project ID:MOST105-2314-B182-047