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.

Abstract: Transgene constructs for generating transgenic animals, wherein the transgene encodes a gene product which modulates transcription of a hypertrophy-sensitive gene, are provided. Further provided are recombinant vectors comprising the transgenes of the invention. Further provided are transgenic animals generated using the transgene constructs. Further provided are enzyme-based, cell-based, and whole-animal-based assays for detecting substances having therapeutic activity toward cardiac hypertrophy. Further provided are compositions comprising substances which modulate levels of active product of a hypertrophy-sensitive gene. Further provided are methods of treating cardiac hypertrophy.

Abstract: Transgene constructs for generating transgenic animals, wherein the transgene encodes a gene product which modulates transcription of a hypertrophy-sensitive gene, are provided. Further provided are recombinant vectors comprising the transgenes of the invention. Further provided are transgenic animals generated using the transgene constructs. Further provided are enzyme-based, cell-based, and whole-animal-based assays for detecting substances having therapeutic activity toward cardiac hypertrophy. Further provided are compositions comprising substances which modulate levels of active product of a hypertrophy-sensitive gene. Further provided are methods of treating cardiac hypertrophy.

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.

Abstract: The present invention relates to compositions and methods relating to MEK5 and its role in heart disease. This protein has now been identified as a target for therapeutic intervention due to its role molecular events that lead to or contribute to cardiac hypertrophy and/or dilated cardiomyopathy. In particular, inhibition of MEK5 activity will lead to decrease signalling of the pathways and reduce or eliminate the effects on sarcomere assembly, which in turn result or contribute to cardiac dysfunction. Also provided are transgenic animals and methods of screening for inhibitors of MEK5.

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.

Abstract: The present invention relates to a novel cardiac-specific transcription factor, myocardin. This molecule modulates the development and differentiation of cardiomyocytes and is a potent inhibitor of cell growth. Methods to exploit these observations are provided and include respecifiying non-cardiac cells into cardiac cells, stimulating cardiac tissue regeneration, and methods for treating cardiomyopathies, myocardial infarction.

Abstract: The present invention discloses new muscle ring finger (MURF) proteins designate MURF-1, MURF-2 and MURF-3. The genes encoding these MURFs also are provided. MURFs interact with microtubules and thus play a role in cytoskeletal function, mitosis and cell growth. Thus, the uses of MURFs in diagnosis, treatment and drug screening, in particular relation to cardiomyopathies, are described.

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 Ca++ stimulation of the hypertrophic response is mediated through MEF2. Thus, the present invention provides methods of treating cardiac hypertrophy as well as transgenic constructs for preparing transgenic animals. Further provided are methods of using the transgenic animals of the present invention, or cells isolated therefrom, for the detection of compounds having therapeutic activity toward cardiac hypertrophy.

Abstract: Transgene constructs for generating transgenic animals, wherein the transgene encodes a gene product which modulates transcription of a hypertrophy-sensitive gene, are provided. Further provided are recombinant vectors comprising the transgenes of the invention. Further provided are transgenic animals generated using the transgene constructs. Further provided are enzyme-based, cell-based, and whole-animal-based assays for detecting substances having therapeutic activity toward cardiac hypertrophy. Further provided are compositions comprising substances which modulate levels of active product of a hypertrophy-sensitive gene. Further provided are methods of treating cardiac hypertrophy.

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 Ca++ stimulation of the hypertroplic response is mediated through MEF2. Thus, the present invention provides methods of treating cardiac hypertrophy as well as transgenic constructs for preparing transgenic animals. Further provided are methods of using the transgenic animals of the present invention, or cells isolated therefrom, for the detection of compounds having therapeutic activity toward cardiac hypertrophy.

Abstract: Transgene constructs for generating transgenic animals, wherein the transgene encodes a gene product which modulates transcription of a hypertrophy-sensitive gene, are provided. Further provided are recombinant vectors comprising the transgenes of the invention. Further provided are transgenic animals generated using the transgene constructs. Further provided are enzyme-based, cell-based, and whole-animal-based assays for detecting substances having therapeutic activity toward cardiac hypertrophy. Further provided are compositions comprising substances which modulate levels of active product of a hypertrophy-sensitive gene. Further provided are methods of treating cardiac hypertrophy.

Abstract: The present invention relates to isolated DNA molecules encoding the murine SM22.alpha. promoter, gene transfer vectors containing the same, and method of use of the same to target gene expression in arterial smooth muscle cells.

Abstract: The present invention relates to isolated DNA molecules encoding the murine SM22.alpha. promoter, gene transfer vectors containing the same, and method of use of the same to target gene expression in arterial smooth muscle cells.