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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.

Discover AnyGenes qPCR array for analyzing Endothelial to Mesenchymal Transition (EndMT) pathways, enabling precise insights into cell signaling and disease mechanisms.

During EndMT, endothelial cells:

  • Downregulate endothelial markers (VE-cadherin, CD31, vWF)
  • Disrupt intercellular junctions and barrier integrity
  • Upregulate mesenchymal markers (α-SMA, vimentin, fibronectin)
  • Acquire migratory and profibrotic behavior

EndMT plays essential roles in:

  • Embryonic cardiovascular development
  • Angiogenesis and wound healing
  • Organ fibrosis
  • Cardiovascular remodeling
  • Cancer progression and stromal activation
  • Pulmonary hypertension

EndMT represents a critical mechanism of vascular plasticity in both physiological and pathological contexts.

Assessing EndMT activity through gene expression profiling

EndMT activity can be efficiently assessed by measuring gene expression changes in:

  • EndMT transcription factors (SNAI1, SNAI2, TWIST1, ZEB1, ZEB2)
  • Endothelial markers (CDH5, PECAM1, VWF)
  • Mesenchymal markers (ACTA2, VIM, FN1, COL1A1)
  • TGF-β and Wnt pathway components
  • Inflammation-associated regulators

Gene expression profiling provides a quantitative and reproducible approach to characterize endothelial plasticity and mesenchymal transition dynamics across experimental models.

Endothelial-To-Mesenchymal Transition Progression
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

EndMT integrates multiple extracellular signals:

Primary inducer of EndMT via SMAD-dependent and SMAD-independent pathways.

Enhances mesenchymal gene expression and synergizes with TGF-β signaling.

Regulates endothelial plasticity through Snail and Twist activation.

Supports survival and mesenchymal transition.

HIF activation and ROS signaling promote EndMT in fibrosis and cancer.

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:

  • Homo sapiens (human)
  • Mus musculus (mouse)
  • Rattus norvegicus (rat)
  • Sus scrofa (pig)

Our solutions enable researchers to:

  • Quantify transcription factor signatures
  • Analyze endothelial–mesenchymal marker balance
  • Study TGF-β, Wnt and Notch pathway activation
  • Investigate inflammation-driven EndMT
  • Generate reproducible, publication-ready data

Customize your own signaling pathways (SignArrays®) with the factors of your choice!
Simply download and complete our Personalized SignArrays® information file and send it at [email protected] to get started on your project.

Frequently asked questions

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 is implicated in cardiac fibrosis, pulmonary fibrosis, renal fibrosis, atherosclerosis, pulmonary hypertension and cancer progression.

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.

  1. Bischoff J.  Endothelial-to-Mesenchymal Transition. Circ Res. (2019);124(8):1163-1165.
  2. Gorelova A,  Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension. Antioxid Redox Signal. (2021);34(12):891-914.
  3. 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.
  4. 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:

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