Abnormal Flow Conditions Promote Endocardial Fibroelastosis Via Endothelial-to-Mesenchymal Transition, Which Is Responsive to Losartan Treatment

•EFE is a congenital cardiac pathology contributing to increased morbidity and mortality. The pathologic triggers of EFE remain to be characterized.•To determine whether abnormal flow promotes EFE development, we used in vivo neonatal rodent surgical models and an in vitro model using human primary endocardial cells•We established novel surgical model with flow profiles seen in patients that develop EFE. Static and turbulent flow conditions promoted EFE development in neonatal rodent hearts.•Losartan treatment is shown to significantly ameliorate EFE progression and decreases mRNA and protein expression of EndoMT markers in neonatal rodent hearts.•RNAseq analysis of human endocardial cells subjected to different flow conditions show that normal flow suppresses gene expression critical for mesenchymal differentiation and Notch signaling.