Open AccessEndothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension
Author(s) -
Anastasia Gorelova,
Mariah Berman,
Imad Al Ghouleh
Publication year - 2021
Publication title -
antioxidants and redox signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.277
H-Index - 190
eISSN - 1557-7716
pISSN - 1523-0864
DOI - 10.1089/ars.2020.8169
Subject(s) - mesenchymal stem cell , reprogramming , hypoxia (environmental) , endothelial dysfunction , context (archaeology) , disease , cardiac fibrosis , fibrosis , pulmonary hypertension , medicine , bmpr2 , inflammation , neuroscience , bioinformatics , bone morphogenetic protein , biology , immunology , pathology , cell , chemistry , paleontology , genetics , organic chemistry , oxygen , biochemistry , gene
Endothelial-to-mesenchymal transition (EndMT) is a process that encompasses extensive transcriptional reprogramming of activated endothelial cells leading to a shift toward mesenchymal cellular phenotypes and functional responses. Initially observed in the context of embryonic development, in the last few decades EndMT is increasingly recognized as a process that contributes to a variety of pathologies in the adult organism. Within the settings of cardiovascular biology, EndMT plays a role in various diseases, including atherosclerosis, heart valvular disease, cardiac fibrosis, and myocardial infarction. EndMT is also being progressively implicated in development and progression of pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH). This review covers the current knowledge about EndMT in PH and PAH, and provides comprehensive overview of seminal discoveries. Topics covered include evidence linking EndMT to factors associated with PAH development, including hypoxia responses, inflammation, dysregulation of bone-morphogenetic protein receptor 2 (BMPR2), and redox signaling. This review amalgamates these discoveries into potential insights for the identification of underlying mechanisms driving EndMT in PH and PAH, and discusses future directions for EndMT-based therapeutic strategies in disease management.