Compositions and methods for monitoring enpp1 activity
AssigneeThe Regents of the University of Californa
InventorArjun Deb
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Abstract
Provided herein are methods and compositions related to monitoring ENPP1 activity and the treatment of cardiac injury using pyrimidine nucleotides.
Claims125
A method of monitoring ENPP1 activity after cardiac injury in a subject comprising determining whether a level of a pyrimidine nucleotide in serum of the subject is below a threshold level, wherein a level of the pyrimidine nucleotide below the threshold level is indicative of ENPP1 activity.
A method of monitoring ENPP1 activity after cardiac injury in a subject, comprising:
- (a) determining a level of a purine nucleotide and/or a purine nucleoside in serum of the subject;
- (b) determining a level of a pyrimidine nucleotide in serum of the subject;
- and
- (c) determining whether a ratio of the level of the purine nucleotide and/or the purine nucleoside to the level of the pyrimidine nucleotide is above a threshold level, wherein a ratio above the threshold level is indicative of ENPP1 activity.
A method of treating myocardial infarction, promoting cardiac wound healing, enhancing cardiac repair, inhibiting ENPP1 activity, and/or preventing heart failure, cardiac cell death, ectopic calcification of cardiac tissue, scarring of cardiac tissue, dilated cardiomyopathy, and/or release of one or more pro-inflammatory molecules from cardiac myocytes in a subject, comprising:
- (a) determining whether serum of the subject comprises a level of a pyrimidine nucleotide below a threshold level;
- and
- (b) if the serum is characterized by a level below the threshold level, administering the pyrimidine nucleotide to the subject.
The method of any one of claims 35-48, further comprising conjointly administering the pyrimidine nucleotide with an additional pyrimidine nucleotide to the subject.
A method of treating myocardial infarction, promoting cardiac wound healing, enhancing cardiac repair, inhibiting ENPP1 activity, and/or preventing heart failure, cardiac cell death, ectopic calcification of cardiac tissue, scarring of cardiac tissue, dilated cardiomyopathy, and/or release of one or more pro-inflammatory molecules from cardiac myocytes in a subject, comprising:
- (a) determining a level of a purine nucleotide and/or a purine nucleoside in serum of the subject;
- (b) determining a level of a pyrimidine nucleotide in serum of the subject;
- (c) determining whether a ratio of the level of the purine nucleotide and/or the purine nucleoside to the level of the pyrimidine nucleotide is above a threshold level;
- and
- (d) if the ratio of the level of the purine nucleotide and/or the purine nucleoside to the level of the pyrimidine nucleotide is above a threshold level, administering the pyrimidine nucleotide to the subject.
A method of identifying a candidate ENPP1 inhibitor, comprising:
- (a) contacting a cell sample with a test agent;
- (b) measuring a level of a pyrimidine nucleotide of the cell sample;
- and
- (c) identifying the test agent as a candidate ENPP1 inhibitor if the level of the pyrimidine nucleotide is increased as compared to a level of the pyrimidine nucleotide of a cell sample not contacted with the test agent.
The method of any one of claims 989-93, wherein the pyrimidine nucleotide is cytidine.
A method of identifying a candidate ENPP1 inhibitor, comprising:
- (a) contacting a cell sample with a test agent;
- (b) measuring a level of a purine nucleotide of the sample;
- (c) measuring a level of a pyrimidine nucleotide of the cell sample;
- (d) determining a ratio of the level of the purine nucleotide to the level of the pyrimidine nucleotide;
- and
- (e) identifying the test agent as a candidate ENPP1 inhibitor if the ratio is decreased as compared to a ratio of the level of the purine nucleotide to the level of the pyrimidine nucleotide of a cell sample not contacted with the test agent.
Dependencies are inferred from the claim text.