Methods of diagnosing atherosclerosis by measuring apoci

Abstract

The present invention provides methods and compositions for identifying compounds which inhibit ApoCI and which are useful in the treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction. The invention further provides methods for treating subjects suffering from or at risk of developing atherosclerosis, plaque rupture, apoptosis, or myocardial infarction. The invention further provides methods for diagnosing subjects at suffering from or at risk of developing treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction.

1 - 16 . (canceled) 
     
     
         17 . A method of identifying a compound useful for the treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction comprising:
 a) contacting ApoCI polypeptide with a test compound; and   b) determining whether the test compound binds to ApoCI,   wherein a test compound that binds to ApoCI is identified as a compound useful for the treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction.   
     
     
         18 . A method of identifying a compound useful for the treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction comprising:
 a) contacting ApoCI polypeptide with a test compound; and   b) determining whether the test compound inhibits ApoCI activity,   wherein a test compound that inhibits ApoCI activity is identified as a compound useful for the treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction.   
     
     
         19 . The method of  claim 18 , wherein ApoCI activity is measured by measuring the ability of ApoCI to activate N-SMase activity. 
     
     
         20 . The method of  claim 18 , wherein ApoCI activity is measured by measuring the ability of ApoCI to inhibit cell surface expression of SR-BI or ABCA1. 
     
     
         21 . The method of  claim 18 , wherein ApoCI activity is measured by measuring the ability of ApoCI to induce apoptosis in a cell. 
     
     
         22 . The method of  claim 21 , wherein the cell is selected from the group consisting of: a vascular smooth muscle cell, an endothelial cell, a macrophage, an epithelial cell, a fibroblast, and a T lymphocyte. 
     
     
         23 . The method of  claim 22 , wherein the cell is an aortic smooth muscle cell. 
     
     
         24 . The method of  claim 21 , wherein apoptosis is measured using a DNA-laddering assay. 
     
     
         25 . The method of  claim 21 , wherein apoptosis is measured using fluorescence microscopy. 
     
     
         26 . The method of  claim 21 , wherein apoptosis is measured by measuring cytochrome c release. 
     
     
         27 . The method of  claim 21 , wherein apoptosis is measured by measuring caspase activation. 
     
     
         28 . The method of  claim 27 , wherein the caspase is caspase-3. 
     
     
         29 . A method of identifying a compound useful for the treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction comprising:
 a) contacting a cell that expresses ApoCI with a test compound; and   b) determining whether the test compound inhibits ApoCI expression,   wherein a test compound that inhibits ApoCI expression is identified as a compound useful for the treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction.   
     
     
         30 . The method of  claim 29 , wherein ApoCI expression is measured by measuring the level of ApoCI mRNA. 
     
     
         31 . The method of  claim 30 , wherein ApoCI mRNA is measured using a method selected from the group consisting of: Northern blotting, primer extension, nuclease protection, and RT-PCR. 
     
     
         32 . The method of  claim 29 , wherein ApoCI expression is measured by measuring the level of ApoCI polypeptide. 
     
     
         33 . The method of  claim 32 , wherein the ApoCI polypeptide is secreted into the culture medium. 
     
     
         34 . The method of  claim 29 , wherein the cell is a liver cell. 
     
     
         35 . The method of  claim 32 , wherein the ApoCI polypeptide is measured using a method selected from the group consisting of: Western blotting, ELISA, RIA, and MALDI-TOF. 
     
     
         36 . The method of  claim 18 , wherein the compound increases HDL metabolism. 
     
     
         37 . A method of treating a subject suffering from or at risk for developing atherosclerosis, plaque rupture, apoptosis, or myocardial infarction comprising administering to the subject a therapeutically effective amount of an ApoCI inhibitor. 
     
     
         38 . A method of increasing HDL metabolism in a subject, comprising administering to the subject a therapeutically effective amount of an ApoCI inhibitor.