ENDOTHELIAL TO MESENCHYMAL TRANSITION

Endothelial To Mesenchymal Transition is a complicated way in which endothelial cells separate from the endothelium and move elsewhere. During this process, these cells lose some of their endothelial qualities and take on the characteristics of mesenchymal cells. This includes gaining the ability to move and contract ^(1,3).

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 ⁽²⁾ .

The EndMT process involves significant changes in the endothelial cell phenotype, both in terms of appearance and function. These changes are evident at the morphological, functional, and molecular levels.

Morphologically, the cells undergo alterations in cell polarity and undergo a remarkable restructuring of the cytoskeleton. At the molecular level, the endothelial cells start expressing genes specific to mesenchymal cells and produce corresponding proteins. This includes α-smooth muscle actin (α-SMA), extra domain A (EDA) fibronectin, N-cadherin, vimentin, fibroblast-specific protein-1 (FSP-1), fibroblast activating protein (FAP), and fibrillar collagens type I and type III.

Concurrently, there is a gradual decrease and eventual loss of endothelial cell-specific proteins. Among them 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. These stimuli activate downstream signaling pathways to induce EndMT. Many researchers have widely reviewed many relevant signaling pathways. The transforming growth factor-beta (TGF-β) signaling pathway considered the most important influencer of EndMT. Particularly the canonical downstream SMAD pathway ⁽⁴⁾.

THE EndMT RELATIONSHIP AND DISEASES

EndMT is involved in crucial stages of embryonic development and is also implicated in the development of different types of diseases, both genetic and acquired. These diseases include cancer, vascular issues, inflammation, and fibrosis. The EndMT also plays a role in cardiovascular conditions like atherosclerosis, pulmonary hypertension, valvular disease, vein graft remodeling, endocardial fibroelastosis, wound healing, and aging…^(1,2,3,4).

(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.

BIOMARKER LIST

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Human Endothelial To Mesenchymal Transition signaling pathway

Signaling Pathways	Product ref	Informations
Endothelial To Mesenchymal Transition	ENDMT1H1	List infos

Species : Mus musculus (mouse)

Mouse Endothelial To Mesenchymal Transition signaling pathway

Signaling Pathways	Product ref	Informations
Endothelial To Mesenchymal Transition	ENDMT1M1	List infos

Species : Rattus norvegicus (rat)

Rat EndMT signaling pathway

Signaling Pathways	Product ref	Informations
Endothelial To Mesenchymal Transition	*******	List In progress...

Species : Sus Scrofa (Pig)

Pig EndMT signaling pathway

Signaling Pathways	Product ref	Informations
Endothelial To Mesenchymal Transition	*******	List In progress...

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