Method of preventing progression of hypertension-induced heart failure with pkc peptides

Abstract

Methods are described for slowing or inhibiting the progression of heart failure in a mammalian subject suffering from chronic hypertension. The methods involve administering an εPKC, β 1 PKC, or βIIPKC peptide inhibitor, examples of which are provided.

1 . A method for slowing or inhibiting the progression of heart failure in a mammalian subject suffering from chronic hypertension, comprising:
 administering to the subject a therapeutically effective amount of a βIIPKC peptide inhibitor from the V5 domain ofβIIPKC, wherein the βIIPKC peptide inhibitor specifically inhibits βIIPKC.   
     
     
         2 . The method of  claim 1 , wherein the βIIPKC peptide inhibitor is at least 80% identical to SEQ ID NO:3. 
     
     
         3 . The method of  claim 1 , wherein the βIIPKC peptide inhibitor comprises βIIV5-3 (SEQ ID NO:3). 
     
     
         4 . The method of  claim 1 , wherein the βIIPKC peptide inhibitor is conjugated to a peptide that increases cellular uptake of the peptide inhibitor. 
     
     
         5 . The method of  claim 4 , wherein the peptide that increases cellular uptake of the peptide inhibitor is a TAT peptide comprising SEQ ID NO:1. 
     
     
         6 . The method of  claim 5 , wherein the TAT peptide consists of SEQ ID NO:1. 
     
     
         7 . The method of  claim 1 , wherein the βIIPKC peptide inhibitor is administered in combination with olmesartan. 
     
     
         8 . The method of  claim 1 , wherein the mammalian subject is a heart transplant patient.