Cardiac fibrosis is the underlying cause for the so-called diastolic dysfunction. Cardiac fibrosis is a process of """"""""scarring"""""""" that results in increased stiffness of the cardiac tissue. Thus, relaxation (diastole) of the heart is disturbed, and the filling of the heart impaired. Until now, specific treatment to target the progression of cardiac fibrosis is not yet available. Fibrosis is considered to follow similar pathways in distinct tissues such as the heart, kidney, lung, skin or liver. Recent studies in the kidney demonstrated that """"""""epithelial-mesenchymal- transition"""""""" (EMT) plays an important role in the progression of fibrosis. EMT is defined as a process in which epithelial cells differentiate into activated fibroblasts. As the endocardial cushion, which consists of mesenchymal cells, evolves via EMT from cells from the endocardium during heart development (regulated by BMPs), we hypothesized that endocardial cells could transdifferentiate into fibroblasts and contribute to cardiac fibrosis. It is one aim of this proposal to study cardiac fibrosis in mice with genetically tagged endothelial cells, in which evidence could be provided that endothelial-mesenchymal-transition exists in the heart.
A second aim i s to investigate EMT of endothelial cells and its regulation in vitro.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL082436-02
Application #
7190546
Study Section
Special Emphasis Panel (ZRG1-DIG-B (21))
Program Officer
Meadows, Tawanna
Project Start
2005-07-27
Project End
2007-06-02
Budget Start
2006-07-27
Budget End
2007-06-02
Support Year
2
Fiscal Year
2006
Total Cost
$50,509
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Zeisberg, Elisabeth M; Potenta, Scott; Xie, Liang et al. (2007) Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts. Cancer Res 67:10123-8
Zeisberg, Elisabeth M; Tarnavski, Oleg; Zeisberg, Michael et al. (2007) Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med 13:952-61