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Fig. 1. Induction of endothelial-cell detachment from endothelial-cell/smooth-muscle-cell co-culture spheroids by pharmacological Tie-2 inhibition. Co-culture spheroids of HUVECs and HUASMCs were treated for 4 hours with 10 nM A-422885.66 and, after fixation, whole-mount stained for CD31. Control co-culture spheroids form an intact monolayer of CD31-positive endothelial cells (A). Inhibition of Tie-2 phosphorylation by A-422885.66 leads to detachment of endothelial cells from the endothelial-cell monolayer, as indicated by holes in the monolayer (B, arrowheads). This process cannot be antagonized by exogenous recombinant Ang-1 (C, arrowheads).





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