Apelin polypeptides
The invention provides modified apelin polypeptides having increased stability, circulating half-life, and/or potency relative to the native apelin-13 polypeptide. Compositions comprising the modified apelin polypeptides and methods of using the polypeptides for treating cardiac disorders, such as heart failure, are also disclosed.
1 . A method for treating a cardiovascular condition in a subject in need thereof comprising administering to the subject an isolated polypeptide comprising the amino acid sequence SEQ ID NO:21, wherein the cardiovascular condition is heart failure or hypertension.
2 . The method of claim 1 , wherein dP/dt max and/or ejection fraction is increased in the subject following administration of the polypeptide.
3 . The method of claim 1 , wherein systolic or diastolic function is improved in the subject following administration of the polypeptide.
4 . The method of claim 1 , wherein the heart failure is heart failure with reduced ejection fraction.
5 . The method of claim 1 , wherein the heart failure is heart failure with preserved ejection fraction.
6 . The method of claim 1 , wherein the heart failure is chronic systolic heart failure or chronic diastolic heart failure.
7 . The method of claim 1 , wherein the heart failure is acute heart failure.
8 . The method of claim 1 , wherein the cardiovascular condition is hypertension.
9 . A method of improving cardiac contractility in a subject having a cardiovascular condition comprising administering to the subject an isolated polypeptide comprising the amino acid sequence SEQ ID NO:21, wherein cardiac contractility is improved in the subject following administration.
10 . A method of increasing ejection fraction in a subject having a cardiovascular condition comprising administering to the subject an isolated polypeptide comprising SEQ ID NO:21, wherein the ejection fraction is increased following administration of the polypeptide.
11 . A method of increasing ejection fraction in a subject in need thereof comprising administering an isolated polypeptide comprising the amino acid sequence SEQ ID NO: 21 to the subject in need thereof.
12 . A method of improving cardiac contractility in a subject in need thereof comprising by administering an isolated polypeptide comprising the amino acid sequence SEQ ID NO: 21, wherein the polypeptide increases dP/dt MAX and/or ejection fraction in the subject following administration.
13 . The method of claim 12 , wherein the polypeptide improves systolic or diastolic function in the subject following administration.