NOTCH Inhibition in the Treatment or Prevention of Atherosclerosis

Abstract

The present invention is directed to methods of treating or preventing atherosclerosis and other cardiovascular diseases by administering agents that inhibit or modulate the NOTCH signaling pathway. In addition, the invention encompasses methods for assaying compounds for their ability to treat atherosclerosis based upon their effects on NOTCH signaling, and for measuring levels of amount, function, or activity of NOTCH pathway components in biological samples.

1 - 21 . (canceled) 
     
     
         22 . A method of treating a patient for a cardiovascular disease, comprising administering systemically or locally to said patient a therapeutically effective amount of a compound that inhibits or modulates the NOTCH signaling pathway. 
     
     
         23 . The method of  claim 22 , wherein said cardiovascular disease is selected from the group consisting of: atherosclerosis; heart attack; restenosis after coronary intervention; failure of vein grafts for coronary bypass surgery or hemodialysis shunts; vasculitis; cardiac damage following acute myocardial infarction; chronic heart failure; arterial or valvular calcification; and stroke. 
     
     
         24 . The method of  claim 23 , wherein said cardiovascular disease is atherosclerosis. 
     
     
         25 . The method of  claim 23 , wherein said compound inhibits or modulates the binding of a NOTCH receptor ligand to any of the NOTCH receptor subtypes, NOTCH-1-NOTCH-4. 
     
     
         26 . The method of  claim 25 , wherein said NOTCH receptor ligand is selected from the group consisting of: Delta-like 1 (Dll1), (Delta-like 3 (Dll3), Delta-like 4 (Dll4), Jagged1, and Jagged2. 
     
     
         27 . The method of  claim 26 , wherein said NOTCH receptor subtype is NOTCH-1. 
     
     
         28 . The method of  claim 26 , wherein said NOTCH receptor subtype is NOTCH-3. 
     
     
         29 . The method of  claim 26 , wherein said compound is administered orally as a capsule, tablet or pill. 
     
     
         30 . The method of  claim 26 , wherein said compound is administered systemically by injection. 
     
     
         31 . The method of  claim 26 , wherein said compound is administered locally by injection. 
     
     
         32 . The method of  claim 25 , wherein said compound is an antibody that blocks the binding of said ligand to a NOTCH receptor subtype. 
     
     
         33 . The method of  claim 32 , wherein said ligand is Delta-like 4 (Dll4). 
     
     
         34 . The method of  claim 33 , wherein said cardiovascular disease is atherosclerosis. 
     
     
         35 . The method of  claim 34 , wherein said compound is an antibody that blocks the binding of Dll4 to NOTCH-1 receptors. 
     
     
         36 . The method of  claim 34 , wherein said compound is an antibody that blocks the binding of Dll4 to NOTCH-2 receptors. 
     
     
         37 . The method of  claim 34 , wherein said compound is an antibody that blocks the binding of Dll4 to NOTCH-3 receptors. 
     
     
         38 . The method of  claim 34 , wherein said compound is an antibody that blocks the binding of Dll4 to NOTCH-4 receptors. 
     
     
         39 . The method of  claim 34 , wherein said compound is administered orally as a capsule, tablet or pill. 
     
     
         40 . The method of  claim 34 , wherein said compound is administered systemically by injection. 
     
     
         41 . The method of  claim 34 , wherein said compound is administered locally by injection.