Soluble endoglin and hypercholesterolemia aggravate endothelial and vessel wall dysfunction in mouse aorta
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F18%3A10382084" target="_blank" >RIV/00216208:11160/18:10382084 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00179906:_____/18:10382084
Výsledek na webu
<a href="http://www.sciencedirect.com/science/article/pii/S0021915018300674" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0021915018300674</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.atherosclerosis.2018.02.008" target="_blank" >10.1016/j.atherosclerosis.2018.02.008</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Soluble endoglin and hypercholesterolemia aggravate endothelial and vessel wall dysfunction in mouse aorta
Popis výsledku v původním jazyce
Background and aims: Increased plasma levels of soluble endoglin (sEng) were detected in patients with endothelial dysfunction-related disorders and hypercholesterolemia. In this study, we hypothesized that high levels of sEng accompanied by mild hypercholesterolemia could aggravate endothelial and vessel wall dysfunction and affect endoglin/eNOS signaling in mouse aorta. Methods: Three-month-old female transgenic mice on CBAxC57BL/6J background, with high levels of sEng (Sol-Eng(+) high HFD), and their littermates with low levels of sEng (Sol-Eng(+) low HFD), were fed a high fat diet for six months. Plasma samples were used for biochemical, ELISA and Luminex analyses of total cholesterol, sEng and inflammatory markers. Functional parameters of aorta were assessed with wire myograph 620M. Western blot analyses of membrane endoglin/eNOS signaling and endothelial dysfunction/inflammation markers in aorta were performed. Results: Functional analysis of aorta showed impaired KCl induced vasoconstriction, endothelial-dependent relaxation after the administration of acetylcholine as well as endothelial-independent relaxation induced by sodium nitroprusside in the Sol-Eng(+) high HFD group compared to the Sol-Eng(+) low HFD group. Ach-induced vasodilation after administration of L-NAME was significantly higher in the Sol-Eng(+) high HFD group compared to the Sol-Eng(+) low HFD group. The expression of endoglin, p-eNOS/eNOS, pSmad2/3/Smad2/3 signaling pathway was significantly lower in the Sol-Eng(+) high HFD group compared to the Sol-Eng(+) low HFD group. Conclusions: The results indicate that long-term hypercholesterolemia combined with high levels of sEng leads to the aggravation of endothelial and vessel wall dysfunction in aorta, with possible alterations of the membrane endoglin/eNOS signaling, suggesting that high levels of soluble endoglin might be considered as a risk factor of cardiovascular diseases.
Název v anglickém jazyce
Soluble endoglin and hypercholesterolemia aggravate endothelial and vessel wall dysfunction in mouse aorta
Popis výsledku anglicky
Background and aims: Increased plasma levels of soluble endoglin (sEng) were detected in patients with endothelial dysfunction-related disorders and hypercholesterolemia. In this study, we hypothesized that high levels of sEng accompanied by mild hypercholesterolemia could aggravate endothelial and vessel wall dysfunction and affect endoglin/eNOS signaling in mouse aorta. Methods: Three-month-old female transgenic mice on CBAxC57BL/6J background, with high levels of sEng (Sol-Eng(+) high HFD), and their littermates with low levels of sEng (Sol-Eng(+) low HFD), were fed a high fat diet for six months. Plasma samples were used for biochemical, ELISA and Luminex analyses of total cholesterol, sEng and inflammatory markers. Functional parameters of aorta were assessed with wire myograph 620M. Western blot analyses of membrane endoglin/eNOS signaling and endothelial dysfunction/inflammation markers in aorta were performed. Results: Functional analysis of aorta showed impaired KCl induced vasoconstriction, endothelial-dependent relaxation after the administration of acetylcholine as well as endothelial-independent relaxation induced by sodium nitroprusside in the Sol-Eng(+) high HFD group compared to the Sol-Eng(+) low HFD group. Ach-induced vasodilation after administration of L-NAME was significantly higher in the Sol-Eng(+) high HFD group compared to the Sol-Eng(+) low HFD group. The expression of endoglin, p-eNOS/eNOS, pSmad2/3/Smad2/3 signaling pathway was significantly lower in the Sol-Eng(+) high HFD group compared to the Sol-Eng(+) low HFD group. Conclusions: The results indicate that long-term hypercholesterolemia combined with high levels of sEng leads to the aggravation of endothelial and vessel wall dysfunction in aorta, with possible alterations of the membrane endoglin/eNOS signaling, suggesting that high levels of soluble endoglin might be considered as a risk factor of cardiovascular diseases.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30104 - Pharmacology and pharmacy
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2018
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Atherosclerosis
ISSN
0021-9150
e-ISSN
—
Svazek periodika
271
Číslo periodika v rámci svazku
April
Stát vydavatele periodika
IE - Irsko
Počet stran výsledku
11
Strana od-do
15-25
Kód UT WoS článku
000428090400003
EID výsledku v databázi Scopus
2-s2.0-85042232760