TY - JOUR
T1 - Expression of antisense to integrin subunit β3 inhibits microvascular endothelial cell capillary tube formation in fibrin
AU - Dallabrida, Susan M.
AU - De Sousa, Michelle A.
AU - Farrell, David H.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2000/10/13
Y1 - 2000/10/13
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M001446200
DO - 10.1074/jbc.M001446200
M3 - Article
C2 - 10922359
AN - SCOPUS:0034644684
SN - 0021-9258
VL - 275
SP - 32281
EP - 32288
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 41
ER -