Expression of antisense to integrin subunit β3 inhibits microvascular endothelial cell capillary tube formation in fibrin

Susan M. Dallabrida, Michelle A. De Sousa, David H. Farrell

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

α(v)β3 antagonists 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 α(v)β3. In an effort to develop an α(v)β3 inhibitor that down-regulates the actual level of α(v)β3, we developed an antisense strategy to inhibit α(v)β3 expression in vitro. β3 antisense expressed in endothelial cells specifically down-regulated α(v)β3 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 α(v)β3 is 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.

Original languageEnglish (US)
Pages (from-to)32281-32288
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number41
DOIs
StatePublished - Oct 13 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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