Endothelial‐to‐mesenchymal transition in cardiovascular diseases: Developmental signaling pathways gone awry

摘要

The process named endothelial‐to‐mesenchymal transition (EndMT) was observed for the first time during the development of the chicken embryo several decades ago. Of interest, accumulating evidence suggests that EndMT plays a critical role in the onset and progression of multiple postnatal cardiovascular diseases. EndMT is controlled by a set of developmental signaling pathways, very similar to the process of epithelial‐to‐mesenchymal transition, which determine the activity of several EndMT transcriptional effectors. Once activated, these EndMT effectors regulate the expression of endothelial‐ and mesenchymal‐specific genes, in part by interacting with specific motifs in promoter regions, eventually leading to the down‐regulation of endothelial‐specific features and acquisition of a fibroblast‐like phenotype. Important technical advances in lineage tracing methods combined with experimental mouse models demonstrated the pathophysiological importance of EndMT for human diseases. In this review, we discuss the major signal transduction pathways involved in the activation and regulation of the EndMT program. Furthermore, we will review the latest discoveries on EndMT, focusing on cardiovascular diseases, and in particular on its role in vascular calcification, pulmonary arterial hypertension, and organ fibrosis. Developmental Dynamics 247:492–508, 2018 . ? 2017 Wiley Periodicals, Inc.