Inhibition of vascular smooth muscle cell proliferation

Abstract

Methods of treating a mammal having a condition characterized by vascular smooth muscle cell proliferation, where the mammal is treated with progesterone or an agonist thereof. Also disclosed are methods of screening compounds useful for inhibiting vascular smooth muscle cell proliferation.

What is claimed is:  
     
         1 . A method of treatment comprising: 
 identifying a mammal that is suspected of having, or at a risk of having, a condition characterized by vascular smooth muscle cell proliferation and that is not being treated with estrogen or an agonist thereof; and    administering to the mammal, in the absence of estrogen or an agonist thereof, an amount of progesterone or an agonist thereof effective to decrease vascular smooth muscle cell proliferation in the mammal.    
     
     
         2 . The method of  claim 1 , wherein the mammal is a man or a premenopausal woman.  
     
     
         3 . The method of  claim 1 , wherein the condition is transplant arteriosclerosis.  
     
     
         4 . The method of  claim 1 , wherein the condition is atherosclerosis.  
     
     
         5 . The method of  claim 1 , wherein the condition is angioplasty restenosis.  
     
     
         6 . The method of  claim 1 , wherein the condition is cardiac vein bypass stenosis.  
     
     
         7 . A method of identifying a compound potentially useful for inhibiting vascular smooth muscle cell proliferation, said method comprising: 
 contacting a progesterone receptor with a test compound; and    determining whether the test compound binds to the receptor, wherein binding of the test compound to the receptor is an indication that the compound is potentially useful for inhibiting vascular smooth muscle cell proliferation.    
     
     
         8 . The method of  claim 7 , wherein the progesterone receptor is in a cell.  
     
     
         9 . The method of  claim 8 , wherein the cell is a mammalian cell.  
     
     
         10 . The method of  claim 9 , wherein the mammalian cell is a vascular smooth muscle cell.  
     
     
         11 . The method of  claim 7 , said method further comprising determining whether the test compound activates a progesterone receptor harbored within a cell, wherein activation of the receptor by the test compound is a further indication that the test compound is potentially useful for inhibiting vascular smooth muscle cell proliferation.  
     
     
         12 . The method of  claim 11 , wherein the cell is a mammalian vascular smooth muscle cell.  
     
     
         13 . The method of  claim 12 , wherein said activation is indicated by a decreased level of cyclin A in the mammalian cell as compared to a control untreated with the test compound.  
     
     
         14 . The method of  claim 12 , wherein said activation is indicated by a decreased level of cyclin E in the mammalian cell as compared to a control untreated with the test compound.  
     
     
         15 . A method of identifying a compound potentially useful for inhibiting vascular smooth muscle cell proliferation, said method comprising: 
 contacting a cell containing a progesterone receptor with a test compound; and    determining whether the test compound activates the receptor, wherein activation of the receptor by the test compound is an indication that the compound is potentially useful for inhibiting vascular smooth muscle cell proliferation.    
     
     
         16 . The method of  claim 15 , wherein the cell is a mammalian cell.  
     
     
         17 . A method of identifying a progesterone receptor-binding compound potentially useful for inhibiting vascular smooth muscle cell proliferation, said method comprising: 
 contacting a mammalian cell containing a progesterone receptor with a test compound that binds the progesterone receptor; and    determining whether proliferation of said mammalian cell is inhibited.    
     
     
         18 . The method of  claim 17 , wherein said mammalian cell is a vascular smooth muscle cell.  
     
     
         19 . A method of identifying a progesterone receptor-binding compound potentially useful for inhibiting vascular smooth muscle cell proliferation, said method comprising: 
 contacting a mammalian cell containing a progesterone receptor with a test compound that binds the progesterone receptor; and    measuring a level of cyclin A in the cell, wherein a decrease of said level as compared to an untreated control is an indication that the test compound is potentially useful for inhibiting vascular smooth muscle cell proliferation.    
     
     
         20 . The method of  claim 19 , wherein the mammalian cell is a vascular smooth muscle cell.  
     
     
         21 . A method of identifying a progesterone receptor-binding compound potentially useful for inhibiting vascular smooth muscle cell proliferation, said method comprising: 
 contacting a mammalian cell containing a progesterone receptor with a test compound that binds the progesterone receptor; and    measuring a level of cyclin E in the cell, wherein a decrease of said level as compared to an untreated control is an indication that the test compound is potentially useful for inhibiting vascular smooth muscle cell proliferation.    
     
     
         22 . The method of  claim 21 , wherein the mammalian cell is a vascular smooth muscle cell.