EndMT

EndMT, or endothelial-to-mesenchymal transition, is a biological process in which endothelial cells lose their characteristic traits and acquire mesenchymal, fibroblast-like properties. It occurs during embryonic development and in adult tissues undergoing remodeling or injury, contributing to the generation of mesenchymal cells from the endothelium.

Mechanistically, EndMT is driven by signaling networks such as TGF-β, often in cooperation with Notch, Wnt, and other pathways. Key transcription factors including SNAI1 (Snail), SNAI2 (Slug), ZEB1/2, and TWIST1 repress endothelial gene programs (for example, CDH5/VE-cadherin and PECAM1) and promote mesenchymal programs (such as ACTA2, Vimentin, and S100A4). EndMT cells typically lose endothelial markers and gain migratory and extracellular matrix–producing capabilities. The process is commonly triggered by inflammatory signals, hypoxia, oxidative stress, and changes in shear stress or the tissue microenvironment.

In development, EndMT contributes to cardiovascular morphogenesis, notably the formation of cardiac cushions and heart valves. In the adult, EndMT is implicated in fibrotic diseases (lung, kidney, liver), vascular remodeling in atherosclerosis and pulmonary hypertension, and the generation of cancer-associated fibroblast populations that can support tumor progression. It also has potential roles in other organ systems and disease contexts.

Detection of EndMT relies on lineage-tracing studies in model organisms and the observation of cells coexpressing endothelial and mesenchymal markers in human tissues. Therapeutically, EndMT is a target of interest for anti-fibrotic and anti-cancer strategies, with approaches aimed at inhibiting TGF-β or related pathways, while avoiding disruption of normal endothelial function and development.