We explored the possibility of using a genetic approach to inhibit integrin-mediated endothelial cell adhesion and survival. We constructed recombinant adenoviruses (Ads) expressing chimeric proteins consisting of the cytoplasmic and transmembrane domains of integrin 1 (CH1), 3 (CH3) or the 1 transmembrane domain alone (CH2) connected to the extracellular domain of L3T4 placed under the control of the CMV promoter (AdCMV) or the endothelial cell specific Tie-1 promoter (AdTie). All constructs were expressed in a dose-and time-dependent manner with over 90% of cells expressing the constructs within 24 h (AdCMVs) or 72 h (AdTies) after infection. Confluent monolayers of HUVEC infected with AdCMVCH1 or AdCMVCH3 detached from the substrate in a time-and dose-dependent manner with over
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