Mus musculus cardiac pressure overload

Cardiac hypertrophy is a response to hemodynamic stress, and is associated with cardiac dysfunction and death. However, whether hypertrophy itself represents a disease process remains unclear. Hypertrophy is driven by changes in myocardial gene expression that require the MEF2 family of DNA-binding transcription factors, as well as the nuclear lysine acetyltransferase p300. In this study we sought to determine the effects of preventing MEF2 acetylation on cardiac adaptation to stress, using a small molecule designed to interfere with MEF2-co-regulator binding and acetylation. The data provided here include RNASeq analysis of left ventricular tissue from mice subjected to surgical pressure overload or a sham operation, and treated with 8MI or its vehicle for 4 weeks. We observed that 8MI transformed the transcriptional response to pressure overload, normalizing almost all 232 genes dysregulated by hemodynamic stress. We conclude that MEF2 acetylation is required for development and maintenance of pathological cardiac hypertrophy, and that blocking MEF2 acetylation can permit recovery from hypertrophy without impairing physiologic adaptation.