MEF2C Protein Isoform Transition to a Repressor Variant is Linked to Development of Heart Failure

The transcription factor MEF2C has been implicated in the pathogenesis of cardiac remodeling and heart failure. The underlying mechanisms of the MEF2C detrimental effects still remain elusive. MEF2C is unique among the MEF2 family in that alternative splice acceptors in the last exon give forms that include or exclude a short domain, which has an inhibitory effect on the MEF2C activity. Objective: To identify if MEF2Cγ+ repressor variant has a role in the cardiac detrimental effects of MEF2C. Conclusions: We conclude that upregulation of MEF2Cγ+ in adult hearts causes cardiac pathogenic features through dysregulation of cell cycle and dedifferentiation of cardiomyocytes. Culture of neonatal rat ventricular cardiomyocytes were treated with adenovirus particles of mef2Cγ+, mef2Cγ- or mef2Cγ+-23/24 or untreated Control. The samples were analyzed in triplicate.