Little definitive information is known concerning how new blood vessels form or regress and it is likely that novel endothelial cell proteins exist which will specifically regulate these uniquely endothelial cell processes. An in vitro model of capillary morphogenesis using human endothelial cells resuspended in three dimensional collagen matrices which recapitulates steps during angiogenesis in endothelial cells has been established. Additionally a model of endothelial cell apoptosis with p53 over expression has also been developed. These models have been used to identify genes differentially expressed during capillary morphogenesis and endothelial apoptosis. A number of genes have been identified that are differentially identify during capillary morphogenesis (CMG) and apoptosis associated processes (AAG). Some of these genes are novel and some are related or identical to known genes. This proposal has three objectives (1) to identify novel capillary morphogenesis genes during VEGF induced angiogenesis in vivo (2) to analyze the expression of nine novel CMGs and several known CMGs isolated from an in vitro capillary formation model during VEGF induced angiogenesis in vivo and (3) to identify known and novel genes that regulate endothelial cell apoptosis during capillary morphogenesis/regression and following p53 induction.
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