Journal
FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.912660
Keywords
endothelial cells; L-NAME; angiotensin II; endothelial-to-mesenchymal transition; reversible EndoMT; endothelial functionality; TGF-beta 1
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Funding
- Kaplan family foundation
- American Heart Association [19TPA34880039, 18IPA34170497]
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Endothelial cells can undergo a transition called endothelial-to-mesenchymal (EndoMT) in response to external stimuli, which is characterized by a change in phenotype. This process has been recognized in both developmental and pathological contexts, including fibrotic diseases. The study presents an in vitro method using L-NAME and Ang II to induce and reversibility of EndoMT in Human umbilical vascular endothelial cells (HUVECs). This method may be useful for drug discovery and development targeting the EndoMT process.
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 N omega-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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