Hdac4 and hdac5 in the regulation of cardiac gene expression

Details Hdac4 and hdac5 in the regulation of cardiac gene expression Hdac4 and hdac5 in the regulation of cardiac gene expression

C - Chemistry, Metallurgy

12

Q

C12Q 1/44 (2006.01) A01K 67/027 (2006.01) A61K 38/46 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2382045

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.

L'invention se rapporte à l'hypertrophie cardiaque. Elle concerne notamment la définition des événements moléculaires reliant la stimulation à l'hypertrophie cardiaque. Plus spécifiquement, les méthodes de l'invention démontrent que la stimulation de Ca?2+¿ de la réponse d'hypertophie est médiée par une interaction de HDAC 4 et 5 avec MEF2, et que la phosphorylation des HDAC induit une perte de répression médiée par HDAC de l'action hypertrophique de MEF2. Ainsi, l'invention porte sur des méthodes et des compositions de traitement de l'hypertrophie cardiaque, ainsi que sur des méthodes et des compositions pour l'identification de personnes sujettes à l'hypertrophie cardiaque. Des méthodes de détection de composés ayant une activité thérapeutique à l'encontre de l'hypertrophie cardiaque sont également décrits.

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