Endothelialtomesenchymal

Endothelial-to-mesenchymal transition (EndMT) is a cellular program in which endothelial cells lose typical endothelial characteristics, such as expression of VE-cadherin and CD31, and acquire mesenchymal traits including a spindle shape, enhanced migratory capacity, and production of extracellular matrix. EndMT contributes to tissue remodeling during development and can be reactivated in injury and disease, potentially generating fibroblast-like cells from the vascular endothelium.

In development, endothelial cells undergo EndMT during embryogenesis, notably in heart development where cells migrate into the cardiac cushions to form valves and contribute to the interstitial cell populations. In adults, EndMT is generally limited but can be induced by injury, inflammation, or pro-fibrotic cues, contributing to scar formation and remodeling.

Mechanisms underlying EndMT involve signaling pathways such as TGF-β, often in crosstalk with BMP, Wnt/β-catenin, Notch, hypoxia, and inflammatory signals. Molecular changes include downregulation of endothelial markers (VE-cadherin, PECAM-1) and upregulation of mesenchymal or myofibroblastic markers (α-smooth muscle actin, S100A4/FSP1, vimentin), along with increased matrix remodeling enzymes.

EndMT is relevant to several physiological and pathological contexts. It contributes to organ fibrosis (heart, kidney, lung), vascular diseases such as atherosclerosis and pulmonary hypertension, and may augment tumor stroma by supplying carcinoma-associated fibroblasts. The extent of its contribution in human disease remains debated, with evidence arising from lineage tracing and single-cell analyses.

Research on EndMT employs lineage tracing in animal models, endothelial cell culture systems, and single-cell RNA sequencing to delineate its occurrence and regulation. Therapeutic strategies aim to limit EndMT by targeting TGF-β or related pathways, seeking to reduce fibrosis while preserving normal vascular function; risks include potential interference with physiological remodeling and repair.