An In Vitro Platform to Study Reversible Endothelial-to-Mesenchymal Transition

Endothelial cells can acquire a mesenchymal phenotype in response to external stimuli through both mechanical and biological factors, using a process known as endothelial-to-mesenchymal (EndoMT) transition. EndoMT is characterized by the decrease in endothelial characteristics, increase in mesenchym...

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Main Authors: Muthu Kumar Krishnamoorthi, Rajarajan A. Thandavarayan, Keith A. Youker, Arvind Bhimaraj
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.912660/full
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author Muthu Kumar Krishnamoorthi
Rajarajan A. Thandavarayan
Keith A. Youker
Arvind Bhimaraj
author_facet Muthu Kumar Krishnamoorthi
Rajarajan A. Thandavarayan
Keith A. Youker
Arvind Bhimaraj
author_sort Muthu Kumar Krishnamoorthi
collection DOAJ
description Endothelial cells can acquire a mesenchymal phenotype in response to external stimuli through both mechanical and biological factors, using a process known as endothelial-to-mesenchymal (EndoMT) transition. EndoMT is characterized by the decrease in endothelial characteristics, increase in mesenchymal markers, and morphological changes. It has been recognized not only during development but also in different pathological conditions including organ/tissue fibrosis in adults. The ability to modulate the EndoMT process could have a therapeutic potential in many fibrotic diseases. An in vitro method is presented here to induce EndoMT with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) and angiotensin II (Ang II) followed by a protocol to study the reversibility of EndoMT. Using this method, we furnish evidence that the combination of L-NAME and Ang II can stimulate EndoMT in Human umbilical vascular endothelial cells (HUVECs) and this process can be reversed as observed using endothelial functionality assays. This method may serve as a model to screen and identify potential pharmacological molecules to target and regulate the EndoMT process, with applications in drug discovery for human diseases.
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spelling doaj.art-9824c119ee5d4d1b80d86585f98d64f72022-12-22T02:38:55ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.912660912660An In Vitro Platform to Study Reversible Endothelial-to-Mesenchymal TransitionMuthu Kumar KrishnamoorthiRajarajan A. ThandavarayanKeith A. YoukerArvind BhimarajEndothelial cells can acquire a mesenchymal phenotype in response to external stimuli through both mechanical and biological factors, using a process known as endothelial-to-mesenchymal (EndoMT) transition. EndoMT is characterized by the decrease in endothelial characteristics, increase in mesenchymal markers, and morphological changes. It has been recognized not only during development but also in different pathological conditions including organ/tissue fibrosis in adults. The ability to modulate the EndoMT process could have a therapeutic potential in many fibrotic diseases. An in vitro method is presented here to induce EndoMT with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) and angiotensin II (Ang II) followed by a protocol to study the reversibility of EndoMT. Using this method, we furnish evidence that the combination of L-NAME and Ang II can stimulate EndoMT in Human umbilical vascular endothelial cells (HUVECs) and this process can be reversed as observed using endothelial functionality assays. This method may serve as a model to screen and identify potential pharmacological molecules to target and regulate the EndoMT process, with applications in drug discovery for human diseases.https://www.frontiersin.org/articles/10.3389/fphar.2022.912660/fullendothelial cellsL-NAMEangiotensin IIendothelial-to-mesenchymal transitionreversible EndoMTendothelial functionality
spellingShingle Muthu Kumar Krishnamoorthi
Rajarajan A. Thandavarayan
Keith A. Youker
Arvind Bhimaraj
An In Vitro Platform to Study Reversible Endothelial-to-Mesenchymal Transition
Frontiers in Pharmacology
endothelial cells
L-NAME
angiotensin II
endothelial-to-mesenchymal transition
reversible EndoMT
endothelial functionality
title An In Vitro Platform to Study Reversible Endothelial-to-Mesenchymal Transition
title_full An In Vitro Platform to Study Reversible Endothelial-to-Mesenchymal Transition
title_fullStr An In Vitro Platform to Study Reversible Endothelial-to-Mesenchymal Transition
title_full_unstemmed An In Vitro Platform to Study Reversible Endothelial-to-Mesenchymal Transition
title_short An In Vitro Platform to Study Reversible Endothelial-to-Mesenchymal Transition
title_sort in vitro platform to study reversible endothelial to mesenchymal transition
topic endothelial cells
L-NAME
angiotensin II
endothelial-to-mesenchymal transition
reversible EndoMT
endothelial functionality
url https://www.frontiersin.org/articles/10.3389/fphar.2022.912660/full
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