Cardiac muscle function and manipulation
A method of causing cardiomyocyte growth and/or differentiation, the method comprising exposing a cardiomyocyte to neuregulin (NRG) thereby activating the MAP kinase pathway in the cardiomyocyte and causing growth and/or differentiation of the cardiomyocyte. Use of neuregulin, neuregulin polypeptide, neuregulin derivatives, or compounds which mimic the activities of neuregulins in the treatment or management of heart disease and heart failure in a mammal.
1 - 21 . (canceled)
22 . A method for treating heart failure in a mammal in need thereof, comprising administering an effective amount of a neuregulin to the mammal, wherein the neuregulin comprises the EGF-like domain of human neuregulin β2 isoform.
23 - 24 . (canceled)
25 . The method of claim 22 , wherein the neuregulin comprises the amino acid sequence of SEQ ID NO:2.
26 . The method of claim 22 , wherein the neuregulin is encoded by the nucleic acid sequence set forth in SEQ ID NO:1.
27 . The method of claim 22 , wherein the mammal is a human.
28 . The method of claim 22 , wherein the heart failure is a disease state selected from the group consisting of congestive heart failure, myocardial infarction, tachyarrhythmia, familial hypertrophic cardiomyopathy, ischaemic heart disease, idiopathic dilated cardiomyopathy and myocarditis.
29 . The method of claim 22 , wherein the heart failure is ischaemic, congenital, rheumatic or idiopathic.
30 . The method of claim 22 , wherein the heart failure results from disassociation of cardiac muscle cell-cell adhesion and/or the disarray of sarcomeric structures in the human.
31 . The method of claim 22 , wherein the heart failure results from an agent that causes cardiac hypertrophy or congestive heart failure.
32 . The method of claim 31 , wherein the agent that causes cardiac hypertrophy or congestive heart failure is fludrocortisone acetate or herceptin.
33 . The method of claim 31 , wherein the neuregulin is administered prior to, during or after exposure to said agent.
34 . The method claim 22 , wherein the neuregulin is administered prior to or after the diagnosis of heart failure in said mammal.
35 . The method of claim 22 , wherein the neuregulin is administered after the mammal has suffered ischemia or heart attack.
36 . The method of claim 22 , wherein administration of the neuregulin maintains left ventricular hypertrophy.
37 . The method of claim 22 , wherein said method prevents progression of myocardial thinning.
38 . The method of claim 22 , wherein administration of the neuregulin inhibits cardiomyocyte apoptosis.
39 . The method of claim 22 , wherein administration of the neuregulin decreases DNA synthesis in cardiac muscle cells.
40 . The method of claim 22 , wherein the neuregulin is administered in an amount of at least 10 −8 M.
41 . The method of claim 22 , wherein the neuregulin is administered with a pharmaceutically acceptable carrier, excipient or stabilizer.
42 . The method of claim 22 , wherein the neuregulin is administered by gene therapy methods.
43 . The method of claim 22 further comprising administering an effective amount of an agent that acts to suppress a hypertrophy induction pathway different from the pathway suppressed by the neuregulin, an angiotensin-converting enzyme (ACE) inhibitor, or an agent for treating hypertension.