Methods and compositions relating to HDAC 4 and 5 regulation of cardiac gene expression
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Abstract
The present invention relates to cardiac hypertrophy. More particularly, the present invention defines the molecular events linking calcium stimulation to cardiac hypertrophy. More specifically, the present invention shows that Ca2+ stimulation of the hypertrophic response is mediated through an HDAC 4 and 5 interaction with MEF2, and that phosphorylation of HDACs results in loss of HDAC-mediated repression of MEF2 hypertrophic action. Thus, the present invention provides methods and compositions of treating cardiac hypertrophy, as well as methods and compositions for identifying subjects at risk for cardiac hypertrophy. Further provided are methods for the detection of compounds having therapeutic activity toward cardiac hypertrophy.
22 Citations
80 Claims
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1-19. -19. (canceled)
- 20. A method for treating cardiac hypertrophy in an animal comprising providing at least one of HDAC 4 or 5 to cardiac tissue in said animal.
- 26. A method for treating cardiac hypertrophy in an animal comprising providing an HDAC 4 or 5 agonist to said animal.
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31. A method for identifying a subject at risk of developing cardiac hypertrophy comprising:
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(a) obtaining a biological sample from said subject; and (b) assessing an HDAC 4 or 5 genotype in cells of said sample. - View Dependent Claims (32, 33, 34, 35, 36, 37)
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38-67. -67. (canceled)
- 68. A method for treating cardiac hypertrophy in an animal comprising providing an inhibitor of HDAC phosphorylation to an animal.
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80-83. -83. (canceled)
Specification