ERG is required for the differentiation of embryonic stem cells along the endothelial lineage.

BACKGROUND: The molecular mechanisms that govern stem cell differentiation along the endothelial lineage remain largely unknown. Ets related gene (ERG) has recently been shown to participate in the transcriptional regulation of a number of endothelial specific genes including VE-cadherin (CD144), endoglin, and von Willebrand's Factor (vWF). The specific role of the ETS factor ERG during endothelial differentiation has not been evaluated. RESULTS: ERG expression and function were evaluated during the differentiation of embryonic stem cells into embryoid bodies (EB). The results of our study demonstrate that ERG is first expressed in a subpopulation of vascular endothelial growth factor receptor 2 (VEGF-R2) expressing cells that also express VE-cadherin. During ES cell differentiation, ERG expression remains restricted to cells of the endothelial lineage that eventually coalesce into primitive vascular structures within embryoid bodies. ERG also exhibits an endothelial cell (EC)-restricted pattern during embryogenesis. To further define the role of ERG during ES cell differentiation, we used a knockdown strategy to inhibit ERG expression. Delivery of three independent shRNA led to 70-85% reductions in ERG expression during ES cell differentiation compared to no change with control shRNA. ERG knockdown was associated with a marked reduction in the number of ECs, the expression of EC-restricted genes, and the formation of vascular structures. CONCLUSION: The ETS factor ERG appears to be a critical regulator of EC differentiation.

Influence of completely supra-annular placement of bioprostheses on exercise hemodynamics in patients with a small aortic annulus.

OBJECTIVE: Aortic valve replacement in patients with a small aortic annulus is often associated with increased pressure gradients. For this reason, prostheses for completely supra-annular placement have been developed. To evaluate the potential benefit of this design, the present study compared the effectiveness of 1 intra-supra-annular bioprosthesis and 3 completely supra-annular bioprostheses in patients with an aortic annulus diameter of 23 mm or less. METHODS: Between August 2000 and December 2004, each of 192 patients requiring aortic valve replacement with an intraoperatively measured aortic annulus diameter of 23 mm or less received one of the following bioprostheses: the stented bovine Sorin Soprano bioprosthesis (n = 28) (Sorin Group, Saluggia, Italy), the Carpentier-Edwards Perimount bioprosthesis (n = 50) (Edwards Lifesciences, Irvine, Calif), the Carpentier-Edwards Perimount Magna bioprosthesis (n = 70) (Edwards Lifesciences), or the stented porcine Medtronic Mosaic (n = 44) (Medtronic Inc, Minneapolis, Minn) bioprosthesis. After 6 months, hemodynamic data at rest and during exercise were obtained by echocardiography in 142 patients. RESULTS: The pericardial valves showed lower mean systolic pressure gradients, larger effective orifice areas and indices, and superior effective orifice fractions than did the porcine valve (P < .05) (Carpentier-Edwards Perimount: 10.9 +/- 3.6 mm Hg, 1.59 +/- 0.41 cm2, 0.9 +/- 0.25 cm2/m2, 41.9% +/- 9.6%; Carpentier-Edwards Perimount Magna 10.1 +/- 3.8 mm Hg, 1.64 +/- 0.38 cm2, 0.93 +/- 0.22 cm2/m2, 45.1% +/- 10.2%; Sorin Soprano 13.5 +/- 5.0 mm Hg, 1.64 +/- 0.32 cm2, 0.92 +/- 0.15 cm2/m2, 45.8% +/- 9.0%; vs Medtronic Mosaic 15.5 +/- 5.2 mm Hg, 1.31 +/- 0.42 cm2, 0.75 +/- 0.24 cm2/m2, 35.2% +/- 10.0%, respectively). The lowest mean systolic pressure gradients were found after the implantation of the Carpentier-Edwards Perimount Magna. Effective orifice areas, indices, and fractions of the pericardial valves did not show significant differences. CONCLUSIONS: In patients with small aortic roots, transvalvular gradients and effective orifice area showed a tendency to superior results in pericardial valves compared with the porcine bioprosthesis. However, the completely supra-annular design does not necessarily lead to superior hemodynamic results compared with the intra-supra-annular position.