Glycogen synthase kinase function in endothelial cells
OwnerKenneth Walshinventor
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Abstract
This invention relates to methods and compositions for modulating endothelial cell viability, endothelial cell migration, and angiogenesis. In particular the invention relates to GSK3 molecules, agents that modify the kinase activity of these molecules, and use of the foregoing in modulating the endothelial cell viability, endothelial cell migration, and angiogenesis.
Claims67
A method for inhibiting angiogenesis comprising:
- administering to a subject in need of such treatment an angiogenesis inhibitor selected from the group consisting of:
- (1) an active glycogen synthase kinase-3 (GSK3) molecule, and (2) a GSK3 kinase activator;
- wherein the angiogenesis inhibitor is administered in an amount effective to inhibit angiogenesis in the subject.
A method for enhancing angiogenesis comprising:
- administering to a subject in need of such treatment an angiogenesis promoter selected from the group consisting of:
- (1) an inactive GSK3 molecule, and (2) a GSK3 kinase inhibitor;
- wherein the angiogenesis promoter is administered in an amount effective to enhance angiogenesis in the subject.
A method for inhibiting an endothelial cell activity, comprising:
- contacting an endothelial cell with an angiogenesis inhibitor in an effective amount to inhibit an endothelial cell activity.
A method for enhancing an endothelial cell activity, comprising:
- contacting an endothelial cell with an angiogenesis promoter in an effective amount to enhance an endothelial cell activity.
A method for inhibiting apoptotic cell death of an endothelial cell, comprising:
- contacting an angiogenesis promoter with an endothelial cell
- wherein the angiogenesis promoter is present in an amount effective to inhibit apoptotic cell death of the endothelial cell.
48 The method of claim 40, wherein the contacting of an angiogenesis promoter with an endothelial cell comprises prophylactic administration of the angiogenesis promoter.
A method of screening for a GSK3 kinase activator that inhibits an endothelial cell activity, comprising:
- contacting a test molecule with an endothelial cell and
- determining whether the test molecule inhibits an endothelial cell activity;
- wherein an inhibition of an endothelial cell activity in the presence of the test molecule indicates that the test molecule is a GSK3 kinase activator.
A method of screening for a GSK3 kinase inhibitor that enhances an endothelial cell activity, comprising:
- contacting a test molecule with an endothelial cell and
- determining whether the test molecule enhances an endothelial cell activity;
- wherein an enhancement of an endothelial cell activity in the presence of the test molecule indicates that the test molecule is a GSK3 kinase inhibitor.
A method for treating a condition associated with increased apoptotic cell death of vascular endothelial cells, comprising:
- administering to a subject in need of such treatment an angiogenesis promoter in an amount effective to inhibit increased apoptotic cell death of the vascular endothelial cells.
Dependencies are inferred from the claim text.