Introduction: Successful postnatal surgical removal of Endocardial Fibroelastosis (EFE) can improve the outcome of Hypoplastic Left Heart Syndrome, one of the severest congenital heart failures by preserving ventricular function and growth potential. It has been shown that the transformation of endothelial to mesenchymal cells (EndMT) leads to the development of EFE tissue. The pathomechanism of EFE is still unknown and was investigated in this study to develop local prenatal treatment options.Methods: Cells from human coronary arteries were used for the experiments as they have the same embryonic origin as endocardial cells. The cells were exposed to 10ng/ml TGF-ß;1, 100 ng/ml rhBMP-7 (=TGF-ß inhibitor), 10 ng/ml TGF-ß1 plus 100 ng/ml rhBMP-7 for 72 hours or exposed to 10% of uniaxial static stretch for 8 hours. Cells treated with media only served as control.Results: The treatment with TGF-ß1 as well as uniaxial static stretch of already 10% changes cell morphology. Uniaxial static stretch is also regulated by TGF-ß shown by the activation of transcriptional factors of the TGF-ß1 pathway (Twist) in the nucleus. The cells did not only express the endothelial marker PECAM1 as in the control but in addition stained for the mesenchymal marker aSMA showing active EndMT. After treating the cells with BMP-7 to inhibit the TGF-ß pathway there were significantly less cells undergoing transformation from an endothelial to a mesenchymal cell.Conclusion: This in vitro model showed that uniaxial static stretch activates the growth factor TGF-ß and induces EndMT which can be inhibited by BMP-7. That information makes it possible to develop therapeutic strategies for local treatment in utero.
