Method for promoting neovascularization

Abstract

The present invention relates to a method for enhancing angiogenic activity to promote neovascularization comprising administering to a subject a formulation comprising a synergistically effective amount of a TWEAK agonist and an angiogenic factor.

1 - 6 . (canceled)  
   
   
       7 . A method for enhancing endothelial cell proliferation in an in vitro culture comprising adding to said culture, a formulation consisting essentially of a synergistically effective amount of a TWEAK agonist and an angiogenic factor.  
   
   
       8 . A method for enhancing angiogenic activity in a mammal to promote neovascularization comprising the step of administering to said mammal a formulation consisting essentially of a synergistically effective amount of a TWEAK agonist and an angiogenic factor sufficient to promote neovascularization.  
   
   
       9 . The methods according to claims  7  or  8 , wherein the angiogenic factor is selected from the group consisting of hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), angiopoietin 1, angiopoietin 2, and monocyte chemotactic protein-1 (MCP-1).  
   
   
       10 . The methods according to claims  7  or  8 , wherein the angiogenic factor is bFGF.  
   
   
       11 . The method of  claim 8 , wherein said method is used in the treatment of a myocardial ischemic condition.  
   
   
       12 . The method of  claim 8 , wherein said method is used to promote wound healing.  
   
   
       13 . The method of  claim 8 , wherein said method is used in the treatment of dermal ulcers, lacerations, burns, or other dermal trauma in said mammal.  
   
   
       14 . The method of  claim 8 , wherein said method is used to promote growth of collateral vasculature after ischemia or recovery of erectile function in said mammal.  
   
   
       15 . A method for in vitro culturing of mammalian cells in an in vitro culture comprising adding to said culture a formulation comprising a TWEAK agonist and an angiogenic factor.  
   
   
       16 . The method of  claim 15 , wherein the mammalian cells are selected from the group consisting of vascular smooth muscle cells, fibroblasts, hematopoietic cells, muscle, myotendonous junction, bone-derived cells, cartilage-derived cells, and other mesenchymal cells.  
   
   
       17 . The method of  claim 15 , wherein the TWEAK agonist and the angiogenic factor are present in a synergistically effective amount.  
   
   
       18 . The method of  claim 15 , wherein the formulation consists of a TWEAK agonist and an angiogenic factor.  
   
   
       19 . The method of  claim 15 , wherein the TWEAK agonist is TWEAK.  
   
   
       20 . The method of  claim 15 , wherein the angiogenic factor is selected from the group consisting of hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), angiopoietin 1, angiopoietin 2, and monocyte chemotactic protein-1 (MCP-1).  
   
   
       21 . The method of  claim 15 , wherein the angiogenic factor is bFGF.  
   
   
       22 . The method of  claim 15 , wherein the TWEAK agonist is TWEAK and the angiogenic factor is bFGF.  
   
   
       23 . A formulation comprising a TWEAK agonist and an angiogenic factor.  
   
   
       24 . The formulation of  claim 23 , wherein the formulation consists of a TWEAK agonist and an angiogenic factor.  
   
   
       25 . The formulation of  claim 23 , wherein the TWEAK agonist and the angiogenic factor are present in a synergistically effective amount.  
   
   
       26 . The formulation of  claim 23 , wherein the TWEAK agonist is TWEAK.  
   
   
       27 . The formulation of  claim 23 , wherein the angiogenic factor is selected from the group consisting of hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), angiopoietin 1, angiopoietin 2, and monocyte chemotactic protein-1 (MCP-1).  
   
   
       28 . The formulation of  claim 23 , wherein the angiogenic factor is bFGF.  
   
   
       29 . The formulation of  claim 23 , wherein the TWEAK agonist is TWEAK and the angiogenic factor is bFGF.  
   
   
       30 . A cell culture comprising: mammalian cells, a cell culture medium, and a combination of a TWEAK agonist and an angiogenic factor, wherein the combination is an amount sufficient to promote angiogenesis.  
   
   
       31 . The cell culture of  claim 30 , wherein the mammalian cells are endothelial cells, vascular smooth muscle cells, fibroblasts, hematopoietic cells, muscle, myotendonous junction, bone-derived cells, cartilage-derived cells, and other mesenchymal cells  
   
   
       32 . The cell culture of  claim 30 , wherein the TWEAK agonist and the angiogenic factor are present in a synergistically effective amount.  
   
   
       33 . The cell culture of  claim 30 , wherein the TWEAK agonist is TWEAK.  
   
   
       34 . The cell culture of  claim 30 , wherein the angiogenic factor is bFGF.  
   
   
       35 . The cell culture of  claim 30 , wherein the TWEAK agonist is TWEAK and the angiogenic factor is bFGF.  
   
   
       36 . A method of identifying inhibitors of TWEAK and bFGF mediated cellular proliferation, the method comprising: 
 culturing endothelial cells in the presence of TWEAK and bFGF;    culturing endothelial cells in the presence of TWEAK, bFGF, and a test compound; and    comparing the amount of endothelial cell proliferation in the cell culture containing the test compound to the amount of proliferation in the cell culture not containing with the test compound, wherein a decrease in proliferation in the culture treated with the test compound indicates that the test compound is an inhibitor of proliferation.    
   
   
       37 . The method of  claim 36 , wherein the test compound is an antibody.