Regulation and role of endoglin in cholesterol-induced endothelial and vascular dysfunction in vivo and in vitro
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F19%3A10400925" target="_blank" >RIV/00216208:11160/19:10400925 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/19:10400925
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=M14WFXnMhf" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=M14WFXnMhf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1096/fj.201802245R" target="_blank" >10.1096/fj.201802245R</a>
Alternative languages
Result language
angličtina
Original language name
Regulation and role of endoglin in cholesterol-induced endothelial and vascular dysfunction in vivo and in vitro
Original language description
Our objective was to investigate the effect of cholesterol [hypercholesterolemia and 7-ketocholesterol (7K)] on endoglin (Eng) expression and regulation with respect to endothelial or vascular dysfunction in vivo and in vitro. In vivo experiments were performed in 2-mo-old atherosclerosis-prone apolipoprotein E-deficient/LDL receptor-deficient (ApoE(-/-)/LDLR(-/-)) female mice and their wild-type C57BL/6J littermates. In in vitro experiments, human aortic endothelial cells (HAECs) were treated with 7K. ApoE(-/-)/LDLR(-/-) mice developed hypercholesterolemia accompanied by increased circulating levels of P-selectin and Eng and a disruption of NO metabolism. Functional analysis of the aorta demonstrated impaired vascular reactivity, and Western blot analysis revealed down-regulation of membrane Eng/Smad2/3/eNOS signaling in ApoE(-/-)/LDLR(-/-) mice. 7K increased Eng expression via Krüppel-like factor 6 (KLF6), liver X nuclear receptor, and NF-kappaB in HAECs. 7K-induced Eng expression was prevented by the treatment with 2-hydroxypropyl-beta-cyclodextrin; 8-{[5-chloro-2-(4-methylpiperazin-1-yl) pyridine-4-carbonyl] amino}-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide; or by KLF6 silencing. 7K induced increased adhesion and transmigration of monocytic human leukemia promonocytic cell line cells and was prevented by Eng silencing. We concluded that hypercholesterolemia altered Eng expression and signaling, followed by endothelial or vascular dysfunction before formation of atherosclerotic lesions in ApoE(-/-)/LDLR(-/-) mice. By contrast, 7K increased Eng expression and induced inflammation in HAECs, which was followed by an increased adhesion and transmigration of monocytes via endothelium, which was prevented by Eng inhibition. Thus, we propose a relevant role for Eng in endothelial or vascular dysfunction or inflammation when exposed to cholesterol.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
The FASEB Journal
ISSN
0892-6638
e-ISSN
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Volume of the periodical
33
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
6099-6114
UT code for WoS article
000466932600025
EID of the result in the Scopus database
2-s2.0-85065469614