Inhibition of histone deacetylase as a treatment for cardiac hypertrophy
AssigneesThe Regents of the University of Colorado, a body corporate, Board of Regents, The University of Texas System
InventorsCarlin Long, Eric N. Olson, Michael Bristow, Timothy A. McKinsey
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Abstract
The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.
Claims50
A method of treating pathologic cardiac hypertrophy and heart failure comprising:
- (a) identifying a patient having pathologic cardiac hypertrophy;
- and
- (b) administering to said patient a histone deacetylase inhibitor.
A method of preventing pathologic cardiac hypertrophy and heart failure comprising:
- (a) identifying a patient at risk of developing pathologic cardiac hypertrophy;
- and
- (b) administering to said patient a histone deacetylase inhibitor.
A method of identifying inhibitors of cardiac hypertrophy comprising:
- (a) providing a histone deacetylase inhibitor;
- (b) treating a myocyte with said histone deacetylase inhibitor;
- and
- (c) measuring the expression of one or more cardiac hypertrophy parameters,
- wherein a change in said one or more cardiac hypertrophy parameters, as compared to one or more cardiac hypertrophy parameters in a myocyte not treated with said histone deacetylase inhibitor, identifies said histone deacetylase inhibitor as an inhibitor of cardiac hypertrophy.
A method of identifying inhibitors of cardiac hypertrophy comprising:
- (a) providing at least one class I and one class II histone deacetylase;
- (b) contacting said histone deacetylases with a candidate inhibitor substance;
- and
- (c) measuring the activity of said histone deacetylases,
- wherein a greater decrease in class I histone deacetylase activity than class II histone deacetylase activity identifies said candidate inhibitor substance as an inhibitor of cardiac hypertrophy.
Dependencies are inferred from the claim text.