Homotypic and heterotypic cell interactions are critical in the assembly and maturation of blood vessels. The aim of this study was to determine the role of Angiopoietin-1 in controlling interaction between endothelial cells and mural cells, and define the classes of molecules involved in mediating this interaction. The influence of heterotypic cell interaction on expression of activin receptor-like kinase 1 (ALK-1) was examined in order to gain insight into the mechanisms of mural cell control of endothelial phenotype. In addition, to begin to explore cell-cell interaction in vessel assembly in vivo attempts were made to establish a non-invasive model for inducing neovessel formation.;Angiopoietin-1 was found to stimulate adhesion between endothelial cells and smooth muscle cells by more than two-fold. This adhesion was calcium-dependent and inclusion RGD-peptides decreased adhesion by 70%, and decreased the effect of Angiopoietin-1 by 66%. Blockade of neural-cadherin (N-cadherin) with cyclic-HAV peptides decreased heterotypic adhesion between endothelial cells and mural cells by 30%. N-cad was found to localise strongly to junctions between smooth muscle cells and homotypic adhesion between these cells was inhibited by inclusion of N-cad-blocking peptides. Previous work suggested ALK-1 expression was modulated by endothelial cell-mural cell contact. No evidence was found for contact-induced changes in expression of ALK-1 under the conditions of this study. An in vivo model for augmenting microvessel number was established in patients with peripheral vascular disease by local application of subcontractile electrical stimulation.;These studies define a direct role for Angiopoietin-1 in control of heterotypic interaction between cells of the vessel wall and show involvement of both integrins and N-cadherin in this interaction. The non-invasive model for increasing neovessel density could be useful for examining capillary stabilisation in vivo in future studies.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:416612 |
| Date | January 2003 |
| Creators | Clover, A. James P. |
| Publisher | University of Leicester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/2381/29426 |
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