Methods and compositions for treating cardiac dysfunctions
OwnerNigel Mackman, Rafal Pawlinski +1inventors
InventorsNigel Mackman, Rafal Pawlinski, Burns C. Blaxall
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Abstract
The present invention provides methods and pharmaceutical compositions for treating or preventing cardiac dysfunctions (e.g., cardiac hypertrophy, cardiac remodeling, or heart failure) in subjects who have or are likely to develop cardiomyopathies. Some of the methods are directed to therapeutic or prophylactic treatment of cardiac dysfunctions in subjects having undergone myocardial injuries such as cardiac ischemia/reperfusion or myocardial infarction. Typically, these methods comprising administering to the subjects a therapeutic composition comprising a compound which can specifically inhibit PAR1 mediated signaling or down-regulate the cellular level of PAR1.
Claims93
A method for treating or preventing a cardiac dysfunction in a subject, comprising administering to a subject a therapeutically effective amount of an antagonist of protease activated receptor 1 (PAR1), thereby treating or preventing cardiac dysfunction in the subject, wherein the subject:
- (a) has or is at risk of developing a cardiomyopathy;
- or
- (b) has undergone a myocardial injury.
A method for treating or preventing hypertrophy in a cardiomyocyte cell or proliferation of a cardiac fibroblast, comprising contacting the cell with an antagonist of protease activated receptor 1 (PAR1), thereby treating or preventing hypertrophy in the cardiomyocyte cell.
The method of claim 64, wherein the PAR1 selective antagonist has a binding affinity for PAR1 that is at least 5-fold stronger than the binding affinity of the PAR1 selective antagonist for any of PAR2, PAR3, and PAR4.
The method of claim 72, wherein the PAR1 antagonist down-regulates the cellular level of PAR1.
A pharmaceutical composition for the treatment or prevention of a cardiovascular dysfunction in a subject, comprising:
- (a) a therapeutically effective dose of a PAR1 antagonist;
- and
- (b) a pharmaceutically acceptable carrier, diluent or excipient in unit dosage form.
Dependencies are inferred from the claim text.