Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2

Endothelial Cell Related Abstracts

2 The Prodomain-Bound Form of Bone Morphogenetic Protein 10 is Biologically Active on Endothelial Cells

Authors: Wei Li, Austin Jiang, Richard M. Salmon, Nicholas W. Morrell

Abstract:

BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality due to impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

Keywords: Signal Transduction, Endothelial Cell, bone morphogenetic protein 10 (BMP10), transforming growth factor beta (TGF-B)

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1 Hybrid Finite Element Model of Mechanical Tests of Endothelial Cells

Authors: Jiri Bursa, Veera Venkata Satya Varaprasad Jakka

Abstract:

Recently a hybrid model of the endothelial cell was created by using the bendo-tensegrity concept to complete the continuum parts of the cell with the cytoskeleton. The model includes a network of actin filaments (AFs) as tension supporting cables and microtubules (MTs) as compression-supporting bended beams. It is created by adopting the geometrical shape of a hexagonal prism with its 12 vertices that results in a nearly isotropic behaviour of the model without any preferred orientation. To achieve the synergistic effect of cytoskeletal components, the elements representing AFs, MTs, and Intermediate filaments (IFs) are connected by sharing the same end nodes at the cell membrane (CM) representing focal adhesions (FAs). The AFs are prestressed (i.e., stressed without application of external load), which is essential for the cell shape stability, while the IFs are wavy, thus not bearing load until straightened. The objective is to perform simulations of mechanical tests (compression, tensile, and shear tests) and validate the model with experimental results to capture the appropriate mechanical responses. The model is intended to be used for assessment of the impact of wall shear stress in arteries on endothelium cells. Endothelial cell dysfunction has been linked to atherosclerosis through their response to hemodynamic forces. Endothelial cells are composed in a monolayer; in this manner, further advances are needed to investigate the perception of loads by a population of cells.

Keywords: Endothelial Cell, finite element model, wall shear stress, prestress, mechanical test, tensegrity

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