Methods for Diagnosing Ischemia

Abstract

This invention provides methods and compositions for diagnosing ischemia, ischemia reference expression profiles, and methods for identifying compounds for treating or preventing ischemia.

1 . A method for diagnosing an ischemia or a predisposition for developing an ischemia, the method comprising: determining a level of expression of a plurality of ischemia-associated genes in a biological sample from a mammalian subject, wherein an increase or decrease of said level compared to a normal control level of said genes indicates that said subject suffers from or is at risk of developing ischemia, wherein said plurality of ischemia-associated genes is selected from the genes set forth in Table 1, 2, 3, 4, 5, 6, or 7. 
     
     
         2 . The method of  claim 1 , wherein said plurality of ischemia-associated genes is selected from the genes set forth in Table 1. 
     
     
         3 . The method of  claim 1 , wherein said increase is at least about 1.3 fold higher than said normal control level and said decrease is at least about 1.3 fold lower than said normal control level. 
     
     
         4 . The method of  claim 3 , wherein at least about a 1.3 fold increase in expression of the following genes: LEPROT, PCGF3, PPP3R1, PVRL2, INSR, BIRC1, TSHZ3, DF, FBN2, IER3, NUMB, and LAK when compared to the normal control level, and at least about a 1.3 fold decrease in expression of the following genes: CD8B1 and RRAS2 when compared to the normal control level indicates that the subject has experienced or is at risk for a cardioembolic stroke. 
     
     
         5 . The method of  claim 3 , wherein at least about a 1.3 fold decrease in expression of the following genes: C21orf7, DAB2, JAM3, ITGA2B, PPBP, SYNJ2, SLC25A37, ZNF185, C7orf41, and LAK when compared to the normal control level indicates that the subject has experienced or is at risk for an atherothrombotic stroke. 
     
     
         6 . The method of  claim 1 , wherein said ischemia is a member selected from the group consisting of: embolic stroke, thrombotic stroke, and transient ischemic attack. 
     
     
         7 . The method of  claim 1 , wherein said ischemia is cardioembolic stroke. 
     
     
         8 . The method of  claim 1 , wherein said ischemia is atherothrombotic stroke. 
     
     
         9 . The method of  claim 1 , wherein said sample is blood. 
     
     
         10 . The method of  claim 1 , wherein said level of expression is determined by detecting hybridization of an ischemia-associated gene probe to a gene transcript of said biological sample. 
     
     
         11 . The method of  claim 10 , wherein said hybridization step is carried out on a nucleic acid array. 
     
     
         12 . An ischemia reference expression profile, comprising a pattern of gene expression of a plurality of the genes set forth in Table 1, 2, 3, 4, 5, 6, or 7. 
     
     
         13 . An ischemia reference expression profile, comprising a pattern of gene expression of a plurality of the genes set forth in Table 1. 
     
     
         14 . The ischemia reference expression profile of  claim 13 , wherein at least about a 1.3 fold increase in expression of the following genes: LEPROT, PCGF3, PPP3R1, PVRL2, INSR, BIRC1, TSHZ3, DF, FBN2, IER3, NUMB, and LAK when compared to the normal control level, and at least about a 1.3 fold decrease in expression of the following genes: CD8B 1 and RRAS2 when compared to the normal control level is a reference expression profile for cardioembolic stroke. 
     
     
         15 . The ischemia reference expression profile of  claim 13 , wherein at least about a 1.3 fold decrease in expression of the following genes: C21orf7, DAB2, JAM3, ITGA2B, PPBP, SYNJ2, SLC25A37, ZNF185, C7orf41, and LAK when compared to the normal control level is a reference expression profile for atherothrombotic stroke. 
     
     
         16 . A method of screening for a compound for treating or preventing ischemia, said method comprising the steps of:
 a) contacting a candidate compound with a cell expressing one or more genes set forth in Table 1, 2, 3, 4, 5, 6, or 7; and   b) selecting a compound that modulates the expression level of one or more genes set forth in Table 1, 2, 3, 4, 5, 6, or 7.   
     
     
         17 . The method of  claim 16 , wherein a compound that decreases the expression of at least one gene selected from the group consisting of: LEPROT, PCGF3, PPP3R1, PVRL2, INSR, BIRC1, TSHZ3, DF, FBN2, IER3, NUMB, and LAK when compared to the normal control level, or increases the expression of at least one gene selected from the group consisting of: CD8B 1 and RRAS2 relative to a control level is identified as a compound useful for treating or preventing ischemia. 
     
     
         18 . The method of  claim 17 , wherein the ischemia is cardioembolic stroke. 
     
     
         19 . The method of  claim 16 , wherein a compound that increases the expression of at least one gene selected from the group consisting of: C21orf7, DAB2, JAM3, ITGA2B, PPBP, SYNJ2, SLC25A37, ZNF185, C7orf41, and LAK is identified as a compound useful for treating or preventing ischemia. 
     
     
         20 . The method of  claim 19  wherein the ischemia is atherothrombotic stroke. 
     
     
         21 . An array comprising a nucleic acid which binds to a plurality of nucleic acid sequences set forth in Table 1, 2, 3, 4, 5, 6, or 7.