Method for Treating Arteriosclerosis

Abstract

The invention relates to a method for identifying substances with antiapoptotic activity, where i) cells which express both CD47 and the integrin α v β 3 are cultured, ii) the cells are caused to produce an apoptosis-inducing substance, and/or a substance or substances which induces/induce apoptosis is/are added, iii) the test substance is added, and iv) the apoptosis rate is measured, and to the substances which can be identified with the method.

1 . A method for treating vascular disorders, the method comprising administering to a subject in need of such treatment an effective amount of a composition comprising
 a pharmaceutically acceptable carrier and   an anti-CD47 antibody that binds to at least one compound selected from the group consisting of TSP-1, CD47 and α v β 3  in such a way that simultaneous binding of TSP-1 to CD47 or α v β 3  is inhibited.   
     
     
         2 . The method of  claim 1 , wherein the anti-CD47 antibody inhibits the simultaneous binding of TSP-1 to CD47 or integrin α v β 3  on surfaces of endothelial cells or corresponding recombinant cells. 
     
     
         3 . The method of  claim 2 , wherein the endothelial cells are selected from the group consisting of human placental endothelial cells (HPEC), bovine aorta endothelial cells (BAEC), porcine brain capillary endothelial cells (PBMEC), hybrid cell lines, and human microvascular endothelial cells. 
     
     
         4 . The method of  claim 1 , wherein the anti-CD47 antibody inhibits the simultaneous binding of TSP-1 to CD47 or integrin α v β 3  on surfaces of smooth muscle cells or fibroblasts. 
     
     
         5 . The method of  claim 1 , wherein the anti-CD47 antibody is BRIC 126. 
     
     
         6 . A method for treating vascular disorders, the method comprising administering to a subject in need of such treatment an effective amount of a composition comprising
 a pharmaceutically acceptable carrier and   an anti-CD47 antibody which can be identified by a method comprising
 (a) culturing cells which express both CD47 and the integrin 
 (b) (i) causing the cells to produce an apoptosis-inducing substance, (ii) adding a substance which simultaneously binds CD47 and the integrin α v β 3 , by culturing under static or turbulent flow conditions, thereby inducing apoptosis, or (iii) both (i) and (ii), 
 (c) adding the anti-CD47 antibody, and 
 (d) determining a change in apoptosis rate by determining the portion of cells with apoptotic nuclei, 
   wherein the anti-CD47 antibody binds to a calcium channel in the cell membrane in such a way that apoptosis-specific calcium influx into the cell is suppressed.   
     
     
         7 . The method of  claim 6 , wherein CD47 is involved in the production of the calcium channel. 
     
     
         8 . The method of  claim 6 , wherein the anti-CD47 antibody inhibits apoptosis-specific calcium influx into endothelial cells or corresponding recombinant cells. 
     
     
         9 . The method of  claim 8 , wherein the endothelial cells are selected from the group consisting of human umbilical vein endothelial cells (HUVEC), human placental endothelial cells (HPEC), bovine aorta endothelial cells (BAEC), porcine brain capillary endothelial cells (PBMEC), hybrid cell lines, and human microvascular endothelial cells (HMVEC). 
     
     
         10 . The method of  claim 6 , wherein the anti-CD47 antibody inhibits apoptosis-specific calcium influx into smooth muscle cells or fibroblasts.