Biomarkers of Mineralocorticoid Receptor Activation

Abstract

The present invention relates to the use of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and/or SERPINA3 as biomarkers of the Mineralocorticoid Receptor (MR) activation in a patient. More particularly, the present invention relates to a method for predicting the responsiveness of a patient to a treatment with a MR antagonist or an aldosterone synthase inhibitor, said method comprising determining in a biological sample obtained from said patient the expression level of the NGAL gene and/or of the SERPINA3 gene.

1 . A method for assessing the Mineralocorticoid Receptor (MR) activation in a patient comprising determining in a biological sample obtained from said patient the expression level of one or two biomarkers selected from the group consisting of the Neutrophil Gelatinase-Associated Lipocalin (NGAL) gene and the SERPINA3 gene. 
     
     
         2 - 15 . (canceled) 
     
     
         16 . The method according to  claim 1  wherein said expression level of said one or two biomarkers is determined by determining the quantity of the one or two biomarkers mRNA and said biological sample is a cell or tissue sample. 
     
     
         17 . The method according to  claim 16  wherein said cell sample is a Peripheral Blood Mononuclear Cell (PBMC) sample or an endothelial cell sample. 
     
     
         18 . The method according to  claim 1  wherein said biological sample is a blood sample, a serum sample, a plasma sample or a urine sample. 
     
     
         19 . The method according to  claim 1  wherein said patient is affected with a cardiovascular disease. 
     
     
         20 . The method according to  claim 1  wherein said patient is affected with congestive heart failure or hypertension. 
     
     
         21 . The method according to  claim 1  wherein said patient has already been treated with a standard treatment selected in the group consisting of angiotensin-converting enzyme inhibitor, diuretics, vasodilators, beta-blockers, digitalis, and anticoagulants. 
     
     
         22 . The method according to  claim 1  wherein said patient is affected with obesity, diabetes, or metabolic syndrome. 
     
     
         23 . A method for predicting the responsiveness of a patient to a treatment with a MR antagonist or an aldosterone synthase inhibitor, said method comprising determining in a biological sample obtained from said patient the expression level of one or two biomarkers selected from the group consisting of the Neutrophil Gelatinase-Associated Lipocalin (NGAL) gene and the SERPINA3 gene. 
     
     
         24 . The method according to  claim 23  wherein said expression level of said one or two biomarkers is determined by determining the quantity of the one or two biomarkers mRNA and said biological sample is a cell or tissue sample. 
     
     
         25 . The method according to  claim 24  wherein said cell sample is a Peripheral Blood Mononuclear Cell (PBMC) sample or an endothelial cell sample. 
     
     
         26 . The method according to  claim 23  wherein said biological sample is a blood sample, a serum sample, a plasma sample or a urine sample. 
     
     
         27 . The method according to  claim 23  wherein said patient is affected with a cardiovascular disease. 
     
     
         28 . The method according to  claim 23  wherein said patient is affected with congestive heart failure or hypertension. 
     
     
         29 . The method according to  claim 23  wherein said patient has already been treated with a standard treatment selected in the group consisting of angiotensin-converting enzyme inhibitor, diuretics, vasodilators, beta-blockers, digitalis, and anticoagulants. 
     
     
         30 . The method according to  claim 23  wherein said patient is affected with obesity, diabetes, or metabolic syndrome. 
     
     
         31 . A method for treating a patient affected with a cardiovascular disease, diabetes, obesity or metabolic syndrome, comprising the step of administering to said patient a MR antagonist or an aldosterone synthase inhibitor, wherein said patient has an expression level of one or two biomarkers selected from the group consisting of the Neutrophil Gelatinase-Associated Lipocalin (NGAL) gene and the SERPINA3 gene, higher than a predetermined value obtained from the general population or from healthy subjects. 
     
     
         32 . A kit comprising:
 a) means for detecting the NGAL protein; and   b) means for detecting the SERPINA3 protein.   
     
     
         33 . A kit according to  claim 32  comprising:
 a) a binding partner of the NGAL protein; and 
 b) a binding partner of the SERPINA3 protein.