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Investigations into the Involvement of Tie2 in Endothelial: Mural Cell Interactions

By Benjamin John Dunmore


The interaction of endothelial cells and mural cells play a critical role in the stabilisation and maturation of the embryonic and postnatal vasculature. Several pathological situations exhibit poor and abnormal endothelial and mural cell association. In this study immunohistochemical analysis revealed dysmorphogenic microvessels within atherosclerotic plaques are lacking mural cells. Similar dysmorphogenic mural cell poor vessels were also observed in human myocardium following laser induced myocardial injury. In both cases elevated VEGF was detected associated with the mural cell poor vessels. To gain insight into the mechanisms controlling mural cell recruitment assays were established to examine directly smooth muscle cell migration and adhesion between smooth muscle cells and endothelial cells in culture. These assays were used to study the involvement of the angiopoietin/Tie2 system in recruitment and retention of mural cells. Ang-l was observed to stimulate endothelial-directed migration of putative mural cell precursors. The ligand also increased adhesion between endothelial cells and smooth muscle cells. To investigate further the possible role of Tie2 in interaction between endothelial cells and mural cells a mutant form of the receptor found in inherited venous malformations (VM) was studied. The form of VM associated with this mutant receptor is characterised by dysmorphogenic, enlarged mural cell vessels. Surprisingly, mutant Tie2 did not inhibit endothelial-induced mural cell migration or adhesion between endothelial cells and mural cells.\ud Taken together these data suggest Tie2 has a role in regulating endothelial:mural cell interaction.\ud Furthermore, the presence of mural cell poor vessels in the atherosclerotic plaque, injured myocardium and inherited VM may reflect escape of these vessels from regression by the presence of survival factors in the case of the plaque and injured myocardium, or constitutive anti-apoptotic signalling from mutant Tie2 in the case of VM

Publisher: University of Leicester
Year: 2004
OAI identifier: oai:lra.le.ac.uk:2381/27747

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