Ubiquitin interacting motif peptides as therapeutics
The present disclosure describes the use peptides of comprising ubiquitin interacting motifs (UIMs) alone or in combination with other agents to treat conditions such as cancer, atherosclerosis and obesity.
1. A method of reducing the risk of myocardial infarction in a subject, treating heart disease in a subject, reducing an atherosclerotic plaque rupture in a subject, reducing the risk of restenosis in a subject, inhibiting atherosclerosis in a subject, reducing vascular inflammation in a subject, or reducing weight in a subject comprising administering to said subject a peptide comprising a ubiquitin interactive motif (UIM)-containing peptide comprising the sequence CKGGRAKDCSGEEELQLQLALAMSKEE (SEQ ID NO: 6).
2. The method of claim 1 , wherein the subject has or is at risk of myocardial infarction, heart disease, atherosclerotic plaque rupture, restenosis, atherosclerosis, or vascular inflammation.
3. The method of claim 1 , wherein the UIM-containing peptide is about 27 to about 50 residues in length.
4. The method of claim 2 , wherein the subject exhibits one or more symptoms of heart disease selected from decreased exercise capacity, decreased blood ejection volume, increased left ventricular end diastolic pressure, increased pulmonary capillary wedge pressure, decreased cardiac output, pathologic cardiac index, increased pulmonary artery pressures, increased left ventricular end systolic and diastolic dimensions, increased left and right ventricular wall stress, or wall tension, decreased quality of life, or increased disease-related morbidity and mortality.
5. The method of claim 2 , further comprising administering to the subject a second anti-atherosclerosis therapy.
6. The method of claim 5 , wherein the second-atherosclerosis therapy is a statin.
7. The method of claim 1 , wherein the subject has excess body fat or is overweight.
8. The method of claim 7 , wherein the subject has class I, class II, or class III obesity.
9. The method of claim 1 , wherein the UIM-containing peptide consists of the sequence CKGGRAKDCSGEEELQLQLLALAMSKEE (SEQ ID NO:6).
10. The method of claim 7 , wherein the UIM-containing peptide is 27 to about 50 residues in length.
11. The method of claim 7 , wherein the subject also suffers from renal disease, cardiovascular disease, diabetes, autoimmune disease, respiratory disease, neurodegenerative disease, liver disease, infectious disease, cancer, or has or will undergo transplant.
12. The method of claim 1 , wherein the subject is a human subject.
13. The method of claim 1 , wherein the administration is intravenous, intra-arterial, intra-nasal, transdermal, or oral.
14. The method of claim 1 , wherein the administration is daily, every other day, weekly, or monthly.