Cardiomyocyte proliferation
AssigneeThe Council of the Queensland Institute of Medical Research
InventorsJames HUDSON, Richard MILLS, Enzo PORRELLO, Gregory QUAIFE-RYAN
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Abstract
Provided herein are in vitro and in vivo methods of inducing cardiomyocyte proliferation by contacting cardiomyocytes with or administering to a subject an effective amount of an agent capable of activating sterol biosynthesis, such as mevalonate biosynthesis. Methods and compositions for regenerating a cardiac tissue in a subject that include administering thereto a therapeutically effective amount of an agent capable of activating sterol biosynthesis in a cardiomyocyte are also provided herein.
Claims23
A method of inducing cardiomyocyte proliferation in vitro, the method including the step of contacting one or a plurality of cardiomyocytes with an effective amount of an agent capable of at least partly activating sterol biosynthesis therein to thereby induce cardiomyocyte proliferation.
A method of inducing cardiomyocyte proliferation in a subject, the method including the step of administering to the subject an effective amount of an agent capable of at least partly activating sterol biosynthesis in a cardiomyocyte to thereby induce cardiomyocyte proliferation in the subject.
A method of regenerating a cardiac tissue in a subject in need thereof, the method including the step of administering to the subject a therapeutically effective amount of an agent capable of at least partly activating sterol biosynthesis in a cardiomyocyte to thereby treat or repair the cardiac damage in the subject.
The method of any one of the preceding claims, wherein the agent is or comprises a p38α inhibitor, a MST1 inhibitor, a TGF-beta receptor inhibitor and/or a BMP receptor inhibitor.
The method of any one of the preceding claims, wherein activating sterol biosynthesis comprises, at least in part, increasing the expression and/or activity of one or more proteins and/or enzymes of, or associated with, sterol biosynthesis.
The method of any one of the preceding claims, wherein the agent is further capable of at least partly modulating the expression and/or activity of a cell cycle protein.
The method or composition of any one of the preceding claims, wherein the agent maintains, at least in part, contractile function of proliferated cardiomyocytes.
A composition for use in regenerating a cardiac tissue in a subject, the composition comprising a therapeutically effective amount of an agent capable of activating sterol biosynthesis and optionally a pharmaceutically acceptable carrier, diluent or excipient.
A method of screening, designing, engineering or otherwise producing an agent for inducing cardiomyocyte proliferation, said method including steps of:
- (a) contacting one or a plurality of cardiomyocytes with a candidate molecule;
- and
- (b) determining whether the candidate molecule is capable of at least partly activating sterol biosynthesis to thereby induce cardiomyocyte proliferation.
Dependencies are inferred from the claim text.