Endothelial to mesenchymal transition, a newly recognized type of cellular transdifferentiation

Endothelial-To-Mesenchymal Transition is a complex cell differentiation process by which endothelial cells detach and migrate away from the endothelium and, to varying degrees, diminish endothelial properties and acquire mesenchymal characteristics and phenotype including the acquisition of cellular motility and contractile properties ^(1,3).

The EndMT process is characterized by profound morphological, functional, and molecular changes in the endothelial cell phenotype. Morphological changes occur through alterations in cell polarity and remarkable restructuring of the cytoskeleton. At the molecular level, endothelial cells initiate the expression of mesenchymal cell-specific genes and the production of their corresponding proteins α-smooth muscle actin (α-SMA), extra domain A (EDA) fibronectin, N-cadherin, vimentin, fibroblast-specific protein-1 (FSP-1; also known as S100A4 protein), fibroblast activating protein (FAP), and fibrillar collagens type I and type III. At the same time, this expression of mesenchymal markers is accompanied by the progressive reduction and the eventual loss of endothelial cell-specific proteins including von Willebrand factor (vWF), CD31/platelet-endothelial cell adhesion molecule-1 (CD31/PECAM-1), and vascular-endothelial cadherin (VE-cadherin) ⁽³⁾.

EndMT can occur under pathological conditions such as inflammation, oxidative stress, high blood sugar, and low sheer stress ⁽⁴⁾.

The EndMT has been shown to participate in very important embryonic developmental processes and also play a role in the pathogenesis of various genetically determined and acquired human diseases, including malignant, vascular, inflammatory and fibrotic disorders and in cardiovascular atherosclerosis, development and progression of pulmonary hypertension (PH), valvular disease, vein graft remodeling, endocardial fibroelastosis , wound healing, aging…^(1,2,3,4).