Compositions and methods for treating cardiovascular disease and myocardial infarction with dipeptidyl peptidase inhibitors or b type natriuretic peptide analogues resistant to prolyl-specific dipeptidyl degradation

Abstract

The present invention describes compositions and methods for treating cardiovascular disease and myocardial infarction using dipeptidyl peptidase inhibitors. Also provided are methods for increasing natriuretic peptide function by administering one or more analogues of B type natriuretic peptide that provide increased stability in the presence of prolyl-specific dipeptidyl peptidases.

We claim: 
     
         1 . A method for the treatment of cardiovascular disease comprising administering to a subject in need of thereof, a therapeutically effective amount of a dipeptidyl peptidase inhibitor. 
     
     
         2 . A method for the treatment of heart failure comprising administering to a subject in need thereof, a therapeutically effective amount of a dipeptidyl peptidase inhibitor. 
     
     
         3 . Use of a dipeptidyl peptidase inhibitor for the manufacture of a medicament for the treatment of cardiovascular disease. 
     
     
         4 . Use of a dipeptidyl peptidase inhibitor for the manufacture of a medicament for the treatment of heart failure. 
     
     
         5 . Use according to  claim 3  or  4 , or method according to  claim 1  or  2 , wherein the dipeptidyl peptidase inhibitor inhibits DPP-IV. 
     
     
         6 . Use according to  claim 3 , or method according to  claim 1 , wherein the cardiovascular disease is stroke. 
     
     
         7 . Use according to  claim 3 , or method according to  claim 1 , wherein the cardiovascular disease is acute myocardial infarction. 
     
     
         8 . Use according to  claim 3 , or method according to  claim 1 , wherein the cardiovascular disease is systemic hypertension. 
     
     
         9 . Use according to  claim 3 , or method according to  claim 1 , wherein the cardiovascular disease is cardiac ischemia. 
     
     
         10 . A pharmaceutical composition comprising a therapeutically effective amount of a dipeptidyl peptidase inhibitor in combination with one or more pharmaceutically acceptable carriers for the treatment of cardiovascular disease. 
     
     
         11 . A pharmaceutical composition comprising a therapeutically effective amount of a dipeptidyl peptidase inhibitor in combination with one or more pharmaceutically acceptable carriers for the treatment of heart failure. 
     
     
         12 . A pharmaceutical composition according to  claim 10  or  11 , wherein the dipeptidyl peptidase inhibitor inhibits DPP-IV. 
     
     
         13 . A method of treating a subject in need of increased natriuretic peptide function, comprising: administering one or more analogues of B-type natriuretic peptide that provide increased stability in the presence of prolyl-specific DPP, relative to B-type natriuretic peptide. 
     
     
         14 . A method according to  claim 13 , wherein said subject suffers from one or more conditions selected from the group consisting of stroke, congestive heart failure, cardiac ischemia, systemic hypertension, and myocardial infarction. 
     
     
         15 . A method according to  claim 13 , further comprising administering one or more inhibitors of prolyl-specific DPP to said subject. 
     
     
         16 . A method according to  claim 13 , further comprising administering one or more inhibitors of neutral endopeptidase to said subject. 
     
     
         17 . A method according to  claim 15 , further comprising administering one or more inhibitors of neutral endopeptidase to said subject.