Microrna mediator of cardiomyopathy and heart failure
AssigneeThe UAB Research Foundation
InventorPatrick K. Umeda
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Abstract
Provided herein is a microRNA, specifically, β-myosin microRNA, compositions comprising β-myosin microRNA and methods of inhibiting or reducing expression of β-myosin microRNA. Also provided are genetically modified cells and animals comprising exogenous β-myosin microRNA. Provided herein are methods of screening for agents that modulate β-myosin microRNA expression. In addition, methods of identifying target genes that are regulated by β-myosin microRNA and methods of modulating such genes are described. Methods of diagnosing or determining whether a subject is at risk for a cardiovascular disorder are also described.
Claims34
An isolated microRNA selected from the group consisting of SEQ ID NO:1 or the complement of SEQ ID NO:2, SEQ ID NO:3 or SEQ ID NO:4.
An isolated microRNA having at least 90% identity to SEQ ID NO:1 or the complement of SEQ ID NO:2, SEQ ID NO:3 or SEQ ID NO:4.
A pharmaceutical composition comprising an isolated microRNA selected from the group consisting of SEQ ID NO:1 or the complement of SEQ ID NO:2, SEQ ID NO:3 or SEQ ID NO:4 and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an isolated microRNA having at least 90% identity to SEQ ID NO:1 or the complement of SEQ ID NO:2, SEQ ID NO:3 or SEQ ID NO:4.
A cell comprising an exogenous β-myosin microRNA.
A cell comprising an exogenous β-myosin microRNA gene encoding a β-myosin microRNA wherein the β-myosin microRNA is overexpressed or not expressed.
A transgenic animal comprising an exogenous β-myosin microRNA.
A method for testing a compound for ameliorating a cardiovascular disease, comprising:
- (a) providing a cell overexpressing β-myosin microRNA;
- (b) contacting the cell with the compound;
- (c) and determining whether expression of β-myosin microRNA is reduced.
A method for testing a compound for ameliorating a cardiovascular disease, comprising:
- (a) providing a transgenic animal overexpressing β-myosin microRNA;
- (b) administering to the animal the compound;
- (c) and determining whether expression of β-myosin microRNA is reduced.
A method of modulating in a cell expression of a target gene associated with a cardiovascular disease, comprising administering a β-myosin microRNA to the cell.
A method of modulating in a subject expression of a target gene associated with a cardiovascular disease, comprising administering a β-myosin microRNA to the subject.
A method of determining whether a gene is regulated by β-myosin microRNA comprising;
- (a) contacting a cell with β-myosin microRNA and
- (b) measuring the expression level of the gene, wherein an increase or descrease in expression level of the gene indicates that the gene is regulated by β-myosin microRNA.
A method of predicting a subject's risk for developing a cardiovascular disease or disorder, comprising:
- (a) obtaining a sample from the subject
- (b) determining the level of expression of β-myosin microRNA, wherein an increase in β-myosin microRNA as compared to control indicates the subject is a risk for developing a cardiovascular disease or disorder.
A method of determining whether a compound is effective in ameliorating a cardiovascular disease or disorder, comprising:
- (a) providing a transgenic animal overexpressing β-myosin microRNA;
- (b) administering to the animal the compound;
- (c) and determining whether expression of β-myosin microRNA is reduced, wherein a reduction in β-myosin microRNA indicates that the compound is effective in ameliorating a cardiovascular disease or disorder.
A method of diagnosing a cardiovascular disease or disorder in a subject, comprising:
- (a) obtaining a sample from the subject;
- (b) determining the level of expression of β-myosin microRNA, wherein an increase in β-myosin microRNA as compared to control indicates the subject has a cardiovascular disease or disorder.
A method of reducing or inhibiting expression of β-myosin microRNA in a cell, comprising contacting the cell with an agent that inhibits β-myosin microRNA expression.
A method of treating a cardiovascular disease or disorder in a subject comprising administering to the subject an agent that inhibits β-myosin microRNA expression.
Dependencies are inferred from the claim text.