Epigenetic reprogramming to prevent genetic cardiomyopathy Comment

Mutations in the gene that codes for lamin A/C (LMNA) are a common cause of adult-onset cardiomyopathy and heart failure. In this issue of the JCI, Guenantin and Jebeniani et al. identify impaired cardiomyocyte development and maturation as a prenatal feature in a model of laminopathy. Cardiomyocytes carrying the Lmna point mutation H222P misexpressed genes involved in the epithelial-mesenchymal transition and showed decreased methylation at the fourth lysine of histone H3 (H3K4). Notably, inhibiting lysine-specific demethylase 1 in the LMNA H222P mouse model treated this congenital form of cardiomyopathy and improved survival in utero. These data highlight early epigenomic modifications in lamin A/C-mediated pathology and indicate a unique therapeutic strategy for cardiomyopathy.

Automated summary

Mutations in the LMNA gene are a common cause of adult-onset cardiomyopathy and heart failure, with a prenatal feature of impaired cardiomyocyte development and maturation identified in a Laminopathy model. Treatment of the LMNA H222P mouse model improved congenital cardiomyopathy and increased survival in utero, presenting a unique therapeutic strategy for cardiomyopathy.