Endothelial to Mesenchymal Transition (EndMT) – Signaling Pathways and Biomarker Analysis
What is Endothelial to Mesenchymal Transition (EndMT)?
Endothelial to mesenchymal transition (EndMT) is a dynamic and reversible cellular process in which endothelial cells lose their vascular identity and acquire mesenchymal characteristics such as enhanced motility, contractility and extracellular matrix production.
EndMT is increasingly recognized as a central mechanism linking vascular dysfunction, organ fibrosis and tumor microenvironment remodeling in chronic diseases.
Gene expression profiling provides a quantitative and reproducible approach to characterize endothelial plasticity and mesenchymal transition dynamics across experimental models.
Sequence of events in the course of EndMT progression. Induction of EndMT-associated transcription factors Snai1, Snai2, Twist-1, Zeb1, and Zeb2 results in progressive loss of endothelial markers PECAM-1 and VE-cadherin, and gain of mesenchymal markers vimentin, fibronectin, SM22α, and α-SMA. α-SMA, alpha-smooth muscle actin; EndMT, endothelial-to-mesenchymal transition; PECAM-1, platelet endothelial cell adhesion molecule; SM22α, transgelin; Snai1, Snail; Snai2, Slug; VE-cadherin, vascular endothelial cadherin
Key biological features of the EndMT process
Loss of endothelial phenotype
Acquisition of mesenchymal contractile traits
Cytoskeletal reorganization
Extracellular matrix deposition
Activation by TGF-β, Wnt, Notch and PI3K-AKT signaling
Strong association with fibrosis and vascular disease
Molecular mechanisms driving Endothelial to Mesenchymal Transition
Transcriptional regulation
EndMT is controlled by master transcription factors:
SNAI1 (Snail)
SNAI2 (Slug)
TWIST1
ZEB1 and ZEB2
These factors repress endothelial genes and activate mesenchymal gene programs.
Loss of endothelial identity
Key endothelial markers that decrease during EndMT:
VE-cadherin (CDH5)
CD31 (PECAM-1)
von Willebrand Factor (vWF)
This leads to endothelial barrier dysfunction and increased permeability.
Acquisition of mesenchymal phenotype
Mesenchymal markers that increase:
α-Smooth Muscle Actin (ACTA2)
Vimentin (VIM)
Fibronectin (FN1)
Collagen type I and III
This transition promotes contractility, matrix deposition and tissue stiffening.
Signaling pathways activating Endothelial to Mesenchymal Transition
TNF-α and IL-1 disrupt endothelial junctions and reinforce mesenchymal traits.
EndMT in disease pathophysiology
Fibrosis
EndMT contributes to fibroblast accumulation and extracellular matrix production in:
Cardiac fibrosis
Pulmonary fibrosis
Renal fibrosis
Persistent EndMT promotes organ dysfunction.
Cardiovascular Diseases
In atherosclerosis and vascular remodeling, EndMT leads to:
Endothelial dysfunction
Vascular stiffening
Intimal thickening
Pulmonary Hypertension
EndMT contributes to vascular wall thickening and pathological remodeling.
Cancer
Within the tumor microenvironment, EndMT:
Promotes stromal activation
Enhances tumor progression
Contributes to therapy resistance
Biomarker profiling of the EndMT pathway
Understanding this endothelial plasticity mechanism at the molecular level is essential for:
Identifying early fibrotic signatures
Characterizing vascular remodeling
Monitoring endothelial dysfunction
Evaluating therapeutic response
Robust biomarker profiling ensures reproducible quantification of endothelial–mesenchymal transition dynamics and supports translational research applications.
EndMT biomarker analysis with AnyGenes®
AnyGenes® provides validated qPCR pathway arrays and fully customizable SignArrays® dedicated to EndMT research in:
EThis endothelial transition process is a reversible cellular process in which endothelial cells lose vascular markers and acquire mesenchymal characteristics such as increased motility, contractility and extracellular matrix production.
EndMT is primarily induced by TGF-β signaling and can be reinforced by Wnt/β-catenin, Notch, PI3K-AKT, inflammatory cytokines, hypoxia and oxidative stress.
In fibrotic diseases, EndMT contributes to fibroblast accumulation and excessive extracellular matrix deposition, promoting organ stiffening and dysfunction.
EndMT activity can be assessed by measuring gene expression changes in endothelial markers (CDH5, PECAM1), mesenchymal markers (ACTA2, VIM, FN1), transcription factors (SNAI1, ZEB1, TWIST1) and pathway components using targeted qPCR arrays.
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Gorelova A, Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension. Antioxid Redox Signal. (2021);34(12):891-914.
Piera-Velazquez S, Jimenez SA. Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases. Physiol Rev. (2019);99(2):1281-1324.
Xu Y, Kovacic JC. Endothelial to Mesenchymal Transition in Health and Disease. Annu Rev Physiol. (2023);85:245-267.
Endothelial to mesenchymal transition biomarker list
You can check the biomarker list included in this pathway, see below: