Method for diagnosing a vascular condition

Abstract

A method for diagnosing hypoxia, endothelial dysfunction, a vascular or circulatory condition of a subject, in which the level of expression of a gene, and/or the level of a metabolite or metabolic by-product in a biological test sample is measured and compared to a control sample so as to assess the vascular condition of the subject, is described.

What is claimed is:  
     
         1 . A method for diagnosing a vascular condition in an individual, comprising the steps of: 
 iii) measuring the quantity of a RTP/Drg1 gene product in at least one biological sample obtained from said individual; and    iv) comparing the measured quantity of said RTP/Drg1 gene product to a standard value for the quantity of RTP/Drg1 gene product in a normal biological sample; wherein    an increase in the measured quantity of said RTP/Drg1 gene product relative to the standard value is indicative of said vascular condition.    
     
     
         2 . The method of  claim 1  wherein said standard value is a measured quantity of said RTP/Drg1 gene product in a different biological sample, said different biological sample being substantially unaffected by a vascular condition associated with a reduction in blood flow.  
     
     
         3 . The method of  claim 2  wherein said the biological sample and said different biological sample are obtained from the same individual.  
     
     
         4 . The method of  claim 3  wherein said different biological sample is obtained prior to the onset of said vascular condition.  
     
     
         5 . The method of  claim 1  wherein said standard value is obtained from a data bank.  
     
     
         6 . The method of  claim 1  wherein said vascular condition is selected from the group consisting of peripheral vascular disease, cancer, preeclampsia, renal failure, erectile dysfunction, abnormal pregnancy, heart disease and stroke.  
     
     
         7 . The method of  claim 1  wherein said gene product is RNA.  
     
     
         8 . The method of  claim 1  wherein said gene product is a polypeptide or an antibody binding fragment thereof.  
     
     
         9 . The method of  claim 1  wherein said biological sample is selected from the group consisting of leukocytes, blood, serum, plasma, saliva, urine and tissue.  
     
     
         10 . A method for detecting hypoxia of endothelial dysfunction in an individual, comprising the steps of: 
 i) measuring the quantity of a RTP/Drg1 gene product in at least one biological sample obtained from said individual; and    ii) comparing the measured quantity of said RTP/Drg1 gene product to a standard value for the quantity of RTP/Drg1 gene product in a normal biological sample; wherein    an increase in the measured quantity of said RTP/Drg1 gene product relative to the standard value is indicative of hypoxia or endothelial dysfunction.    
     
     
         11 . The method of  claim 10  wherein said standard value is a measured quantity of said RTP/Drg1 gene product in a different biological sample, said different biological sample being substantially unaffected by hypoxia or endothelial dysfunction.  
     
     
         12 . The method of  claim 11  wherein said the biological sample and said different biological sample are obtained from the same individual.  
     
     
         13 . The method of  claim 12  wherein said different biological sample is obtained prior to the onset of hypoxia or endothelial dysfunction.  
     
     
         14 . The method of  claim 10  wherein said standard value is obtained from a data bank.  
     
     
         15 . The method of  claim 10  wherein said gene product is RNA.  
     
     
         16 . The method of  claim 10  wherein said gene product is a polypeptide or an antibody binding fragment thereof.  
     
     
         17 . The method of  claim 10  wherein said biological sample is selected from the group consisting of leukocytes, blood, serum, plasma, saliva, urine and tissue.  
     
     
         18 . A method for detecting hypoxia or endothelial dysfunction in an individual, comprising the steps of: 
 i) measuring the quantity of a PAI-1 gene product in at least one biological sample obtained from said individual; and    ii) comparing the measured quantity of said PAI-1 gene product to a standard value for the quantity of PAI-1 gene product in a normal biological sample; wherein    an increase in the measured quantity of said PAI-1 gene product relative to the standard value is indicative of hypoxia or endothelial dysfunction.    
     
     
         19 . The method of  claim 18  wherein said standard value is a measured quantity of said PAI-1 gene product in a different biological sample, said different biological sample being substantially unaffected by hypoxia or endothelial dysfunction.  
     
     
         20 . The method of  claim 19  wherein said the biological sample and said different biological sample are obtained from the same individual.  
     
     
         21 . The method of  claim 20  wherein said different biological sample is obtained prior to the onset of said hypoxia or endothelial dysfunction.  
     
     
         22 . The method of  claim 18  wherein said standard value is obtained from a data bank.  
     
     
         23 . The method of  claim 18  wherein said gene product is RNA.  
     
     
         24 . The method of  claim 18  wherein said gene product is a polypeptide or an antibody binding fragment thereof.  
     
     
         25 . The method of  claim 18  wherein said biological sample is selected from the group consisting of leukocytes, blood, serum, plasma, saliva, urine and tissue.  
     
     
         26 . A method for detecting hypoxia or endothelial dysfunction in an individual, comprising the steps of: 
 i) measuring the quantity of a uPAR gene product in at least one biological sample obtained from said individual; and    ii) comparing the measured quantity of said uPAR gene product to a standard value for the quantity of uPAR gene product in a normal biological sample; wherein    an increase in the measured quantity of said uPAR gene product relative to the standard value is indicative of hypoxia or endothelial dysfunction.    
     
     
         27 . The method of  claim 26  wherein said standard value is a measured quantity of said uPAR gene product in a different biological sample, said different biological sample being substantially unaffected by hypoxia or endothelial dysfunction.  
     
     
         28 . The method of  claim 17  wherein said the biological sample and said different biological sample are obtained from the same individual.  
     
     
         29 . The method of  claim 28  wherein said different biological sample is obtained prior to the onset of hypoxia or endothelial dysfunction.  
     
     
         30 . The method of  claim 26  wherein said standard value is obtained from a data bank.  
     
     
         31 . The method of  claim 26  wherein said gene product is RNA.  
     
     
         32 . The method of  claim 26  wherein said gene product is a polypeptide or an antibody binding fragment thereof.  
     
     
         33 . The method of  claim 26  wherein said biological sample is selected from the group consisting of leukocytes, blood, serum, plasma, saliva, urine and tissue.  
     
     
         34 . A method for detecting hypoxia or endothelial dysfunction in an individual, comprising the steps of: 
 i) measuring the quantity of an arginine metabolite in at least one biological sample obtained from said individual; and    ii) comparing the measured quantity of said arginine metabolite to a standard value for the quantity of said arginine metabolite in a normal biological sample; wherein    an increase in the measured quantity of said arginine metabolite relative to the standard value is indicative of hypoxia or endothelial dysfunction.    
     
     
         35 . The method of  claim 28  wherein said arginine metabolite is ADMA or L-NMMA.  
     
     
         36 . A method of assessing an individual's risk for a vascular condition comprising the steps of: 
 i) measuring the quantity of a RTP/Drg1 gene product in at least one biological sample obtained from said individual; and    ii) comparing the measured quantity of said RTP/Drg1 gene product to a standard value for the quantity of RTP/Drg1 gene product in a normal biological sample; wherein    an increase in the measured quantity of said RTP/Drg1 gene product relative to the standard value is indicative of risk for said vascular condition, and said risk correlates with the degree to which said RTP/Drg1 gene product is elevated.    
     
     
         37 . A method for detecting hypoxia or endothelial dysfunction in an individual, comprising the steps of: 
 i) isolating cells from said individual;    ii) measuring the invasiveness or of said cells in an in vitro cellular invasion assay; and    iii) comparing the measured value to a standard value for said cells; wherein an increase in invasiveness relative to said standard is indicative of hypoxia or endothelial dysfunction.    
     
     
         38 . A method for assessing an individual's risk for metastasis, comprising the steps of: 
 i) isolating cells from said individual;    ii) measuring the invasiveness of said cells in an in vitro cellular invasion assay; and    iii) comparing the measured value to a standard value for said cells; wherein an increase in invasiveness relative to said standard is indicative of an increased risk for metastasis.    
     
     
         39 . A method for assessing an individual's risk for metastasis, comprising the steps of: 
 i) measuring the quantity of at least one substance in at least one biological sample obtained from said individual; and    ii) comparing the measured quantity of said substance to a standard value for the quantity of said substance in a normal biological sample; wherein    an increase in the measured quantity of said substance relative to the standard value is indicative of an increased risk for metastasis.    
     
     
         40 . The method of  claim 39  wherein said substance is selected from the group consisting of a RTP/Drg1 gene product, a uPAR gene product, a PAI-1 gene product and an arginine metabolite.  
     
     
         41 . The method of  claim 40  wherein said biological sample consists of non-cancerous cells.  
     
     
         42 . A method for diagnosing a vascular condition in an individual, comprising the step of: 
 i) detecting at least one endocrine disrupter in at least one biological sample obtained from said individual; wherein    the presence of said endocrine disrupter is indicative of said vascular condition.    
     
     
         43 . The method of  claim 42  wherein said endocrine disrupter is p,p-DDE.  
     
     
         44 . The method of  claim 43  wherein said vascular condition is erectile dysfunction.  
     
     
         45 . A method for assessing an individual's risk for contracting a vascular condition, comprising the steps of: 
 i) measuring the quantity of at least one endocrine disrupter in at least one biological sample obtained from said individual;    ii) measuring the quantity of an endogenous hormone in said biological sample; and    iii) determining the ratio of said disrupter to said endogenous hormone in said biological sample; wherein    the risk is proportional to said ratio.    
     
     
         46 . The method of  claim 45  wherein said endocrine disrupter is p,p-DDE and said endogenous hormone is testosterone.  
     
     
         47 . The method of  claim 46  wherein said vascular disorder is erectile dysfunction.  
     
     
         48 . A method of diagnosing a vascular condition in an individual, comprising the steps of: 
 i) measuring the quantity of at least two substances chosen from the group consisting of a product of the RTP/Drg1 gene, a product of the uPAR gene, a product of the PAI-1 gene and a product of abnormal arginine metabolism, in at least one biological sample obtained from said individual; and    ii) comparing the measured quantity of said substances to a standard value for the quantity of said substances in a normal biological sample; wherein    an increase in the measured quantity of at least one of said substances relative to the standard value is indicative of said vascular condition.    
     
     
         49 . The method of  claim 48  further comprising 
 i) isolating cells from said individual;  
 ii) measuring the invasiveness of said cells in an in vitro cellular invasion assay; and  
 iii) comparing the measured value to a standard value for said cells; wherein an increase in invasiveness or an increase in the measured quantity of at least one of said substances relative to the standard value is indicative of said vascular condition.  
 
     
     
         50 . A method of diagnosing hypoxia or endothelial dysfunction in an individual, comprising the steps of: 
 i) measuring the quantity of at least two substances chosen from the group consisting of a product of the RTP/Drg1 gene, a product of the uPAR gene, a product of the PAI-1 gene and a product of abnormal arginine metabolism, in at least one biological sample obtained from said individual; and    ii) comparing the measured quantity of said substances to a standard value for the quantity of said substances in a normal biological sample; wherein    an increase in the measured quantity of at least one of said substances relative to the standard value is indicative of said hypoxia or endothelial dysfunction.