Method of modulating neovascularization

Abstract

The invention provides a method of inhibiting neovascularization in a subject. The method comprises administering to the subject an agent that interferes with fibronectin (Fn) matrix assembly in an amount effective to inhibit neovascularization. The invention also provides a method of identifying an agent that inhibits neovascularization. The method comprises detecting fibronectin (Fn) matrix assembly by stimulated endothelial cells cultured in three-dimensional culture gel in the presence and absence of an agent. A decrease in Fn matrix assembly in the presence of the agent compared to Fn matrix assembly in the absence of the agent is indicative of an agent that inhibits neovascularization. Alternatively, the method of identifying an agent that inhibits neovascularization comprises detecting changes in nuclear architecture in stimulated endothelial cells cultured in three-dimensional culture gel in the presence and absence of an agent. A reduction in nuclear architecture organization identifies an agent that inhibits neovascularization.

What is claimed: 
     
         1 . A method of inhibiting neovascularization in a subject, the method comprising administering to the subject an agent that interferes with fibronectin (Fn) matrix assembly in an amount effective to inhibit neovascularization. 
     
     
         2 . The method of  claim 1 , wherein the agent does not promote apoptosis. 
     
     
         3 . The method of  claim 1 , wherein the agent does not interfere with binding between integrins and soluble Fn. 
     
     
         4 . The method of  claim 1 , wherein the agent comprises an antibody or fragment thereof that binds Fn. 
     
     
         5 . The method of  claim 4 , wherein the antibody or fragment thereof binds Fn at or near Fn III 1,2  modules. 
     
     
         6 . The method of  claim 1 , wherein the agent comprises an Fn fragment. 
     
     
         7 . The method of  claim 6 , wherein the Fn fragment interferes with polymerization of intact Fn dimers. 
     
     
         8 . The method of  claim 6 , wherein the agent is comprises a nucleic acid sequence encoding an Fn fragment. 
     
     
         9 . The method of  claim 1 , wherein the agent comprises a microbial surface component reorganizing adhesive matrix molecule (MSCRAMM). 
     
     
         10 . The method of  claim 9 , wherein the agent comprises a functional upstream domain (FUD) of  Streptococcus pyogenes  adhesion F1 protein. 
     
     
         11 . The method of  claim 10 , wherein the agent is a nucleic acid comprising a nucleic acid sequence encoding a FUD of  Streptococcus pyogenes  adhesion F1 protein. 
     
     
         12 . A method of identifying an agent that inhibits neovascularization, the method comprising detecting fibronectin (Fn) matrix assembly by stimulated endothelial cells cultured in three-dimensional culture gel in the presence and absence of an agent, wherein a decrease in Fn matrix assembly in the presence of the agent compared to Fn matrix assembly in the absence of the agent is indicative of an agent that inhibits neovascularization. 
     
     
         13 . A method of identifying an agent that inhibits neovascularization, the method comprising detecting changes in nuclear architecture in stimulated endothelial cells cultured in three-dimensional culture gel in the presence and absence of an agent, wherein a reduction in nuclear architecture organization identifies an agent that inhibits neovascularization.