Method of preventing progression of hypertension-induced heart failure with PKC peptides
View Patent ↗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, β1PKC, 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 βII Protein Kinase C (βIIPKC) peptide inhibitor from the V5 domain of βIIPKC, wherein the βIIPKC peptide inhibitor specifically inhibits βIIPKC, and wherein the βIIPKC peptide inhibitor is a polypeptide having at least 80% sequence identity to the polypeptide of SEQ ID NO:3.
2. The method of claim 1 , wherein the βIIPKC peptide inhibitor consists of βIIV5-3 (SEQ ID NO:3).
3. The method of claim 1 , wherein the βIIPKC peptide inhibitor is conjugated to a peptide that increases cellular uptake of the peptide inhibitor.
4. The method of claim 3 , wherein the peptide that increases cellular uptake of the peptide inhibitor is a TAT peptide comprising the polypeptide of SEQ ID NO:1.
5. The method of claim 4 , wherein the TAT peptide consists of the polypeptide of SEQ ID NO:1.
6. The method of claim 1 , wherein the βIIPKC peptide inhibitor is administered in combination with olmesartan.
7. The method of claim 1 , wherein the mammalian subject is a heart transplant patient.