The present invention provides methods of treating and preventing cardiac hypertrophy and heart failure. Further provided are transgenic animals exhibiting altered expression of the atypical cadherin Fat4 and methods using said transgenic animals, or cells isolated therefrom, for the detection of compounds having therapeutic activity toward cardiac hypertrophy or regeneration. Embodiments of the present invention provide methods and composition for therapeutic intervention in cardiac hypertrophy or heart repair by modulating Fat4 and/or Amotl1 (angiomotin-like1). Treatment may include deleting Yap or administering verteporfm. Embodiments of the present invention define the molecular events linking Fat4 and Amotl1 to cardiac growth, and show that Fat4 is required to restrict cardiomyocyte hypertrophy and cardiomyocyte proliferation and that this is mediated by Amotl1.
