Introduction: Endothelial-Mesenchymal Transition (EndMT) is a specific form of endothelial dysfunction wherein endothelial cells acquire a mesenchymal phenotype and lose their endothelial functions. We, and others, recently described that EndMT contributes to intimal hyperplasia and atherosclerosis. Pro-fibrotic and inflammatory cytokines, such as IL-1β and TGFβ2 induce EndMT. We found that the mitogen activated protein kinase 7 (MAPK7, also known as Erk5) inhibits EndMT. MAPK7 activation decreases the expression of the histone methyltransferase Enhancer-of-Zeste homologue 2 (Ezh2) thereby maintaining endothelial quiescence.This decrease in Ezh2 expression may therefore be responsible for the protective effects of MAPK7 activation and may t...