Expression of Antisense to Integrin Subunit β3Inhibits Microvascular Endothelial Cell Capillary Tube Formation in Fibrin

• Published in: The Journal of biological chemistry 2000-10, Vol.275 (41), p.32281-32288
• Main Authors: Dallabrida, Susan M., De Sousa, Michelle A., Farrell, David H.
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M001446200

αvβ3antagonists are potent angiogenesis inhibitors, and several different classes of inhibitors have been developed, including monoclonal antibodies, synthetic peptides, and small organic molecules. However, each class of inhibitor works by the same principal, by blocking the binding of ligands to αvβ3. In an effort to develop an αvβ3 inhibitor that down-regulates the actual level of αvβ3, we developed an antisense strategy to inhibit αvβ3 expression in vitro. β3 antisense expressed in endothelial cells specifically down-regulated αvβ3 and inhibited capillary tube formation, with the extent of down-regulation correlating with the extent of tube formation inhibition. This inhibition was matrix-specific, since tube formation was not inhibited in Matrigel. These findings support the notion that αvβ3is required for an essential step of angiogenesis in fibrin, namely capillary tube formation. These results suggest that pseudogenetic inhibition of β3 integrins using antisense techniques may ultimately provide a therapeutic means to inhibit angiogenesis in vivo.