Methods of modulating angiogenesis
AssigneeJoslin Diabetes Center, Inc.
InventorsChristian Rask MADSEN, George Liang KING
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Abstract
The present inventors discovered that PKCε is necessary for VEGF signaling through PI3K/Akt-dependent pathways and is involved in MAPK-dependent pathways, thus regulating eNOS activity and DNA synthesis, respectively. Thus differential manipulation of PKCε activity can be used to modify VEGF effects in conditions in which modulation of angiogenesis is desirable (e.g., for treatment of diabetic proliferative retinopathy or to enhance angiogenesis for treatment of peripheral and myocardial ischemia).
Claims25
A method of inhibiting angiogenesis in a subject, the method comprising administering to the subject a therapeutically effective amount of a composition comprising an inhibitor that specifically inhibits protein kinase C epsilon (PKCε).
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16-21. (canceled)
A method of identifying a candidate compound for modulating angiogenesis in a tissue, the method comprising:
- providing a sample comprising PKCε;
- contacting the sample with a test compound;
- and
- evaluating an effect of the test compound on levels or activity of the PKCε in the sample,
- wherein a test compound that decreases levels or activity of PKCε in the sample is a candidate compound for inhibiting angiogenesis and a compound that increases levels or activity of PKCε in the sample is a candidate compound for enhancing angiogenesis.
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30-34. (canceled)
Dependencies are inferred from the claim text.