Long term effects of soluble endoglin and mild hypercholesterolemia in mice hearts
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F20%3A10417077" target="_blank" >RIV/00216208:11160/20:10417077 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00179906:_____/20:10417077
Výsledek na webu
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FlUtR53iO_" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FlUtR53iO_</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1371/journal.pone.0233725" target="_blank" >10.1371/journal.pone.0233725</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Long term effects of soluble endoglin and mild hypercholesterolemia in mice hearts
Popis výsledku v původním jazyce
Soluble endoglin (sEng) released into the circulation was suggested to be related to cardiovascular based pathologies. It was demonstrated that a combination of high sEng levels and long-term exposure (six months) to high fat diet (HFD) resulted in aggravation of endothelial dysfunction in the aorta. Thus, in this study, we hypothesized that a similar experimental design would affect the heart morphology, TGF beta signaling, inflammation, fibrosis, oxidative stress and eNOS signaling in myocardium in transgenic mice overexpressing human sEng. Three-month-old female transgenic mice overexpressing human sEng in plasma (Sol-Eng(+) high) and their age-matched littermates with low levels of human sEng (Sol-Eng(+) low) were fed a high-fat diet containing 1.25% of cholesterol and 40% of fat for six months. A blood analysis was performed, and the heart samples were analyzed by qRT-PCR and Western blot. The results of this study showed no effects of sEng and HFD on myocardial morphology/hypertrophy/fibrosis. However, the expression of pSmad2/3 and p-eNOS was reduced in Sol-Eng(+) high mice. On the other hand, sEng and HFD did not significantly affect the expression of selected members of TGF beta signaling (membrane endoglin, TGF beta RII, ALK-5, ALK-1, Id-1, PAI-1), inflammation (VCAM-1, ICAM-1), oxidative stress (NQO1, HO-1) and heart remodeling (PDGF beta, COL1A1, beta-MHC). In conclusion, the results of this study confirmed that sEng, even combined with a high-fat diet inducing hypercholesterolemia administered for six months, does not affect the structure of the heart with respect to hypertrophy, fibrosis, inflammation and oxidative stress. Interestingly, pSmad2/3/p-eNOS signaling was reduced in both the heart in this study and the aorta in the previous study, suggesting a possible alteration of NO metabolism caused by six months exposure to high sEng levels and HFD. Thus, we might conclude that sEng combined with a high-fat diet might be related to the alteration of NO production due to altered pSmad2/3/p-eNOS signaling in the heart and aorta.
Název v anglickém jazyce
Long term effects of soluble endoglin and mild hypercholesterolemia in mice hearts
Popis výsledku anglicky
Soluble endoglin (sEng) released into the circulation was suggested to be related to cardiovascular based pathologies. It was demonstrated that a combination of high sEng levels and long-term exposure (six months) to high fat diet (HFD) resulted in aggravation of endothelial dysfunction in the aorta. Thus, in this study, we hypothesized that a similar experimental design would affect the heart morphology, TGF beta signaling, inflammation, fibrosis, oxidative stress and eNOS signaling in myocardium in transgenic mice overexpressing human sEng. Three-month-old female transgenic mice overexpressing human sEng in plasma (Sol-Eng(+) high) and their age-matched littermates with low levels of human sEng (Sol-Eng(+) low) were fed a high-fat diet containing 1.25% of cholesterol and 40% of fat for six months. A blood analysis was performed, and the heart samples were analyzed by qRT-PCR and Western blot. The results of this study showed no effects of sEng and HFD on myocardial morphology/hypertrophy/fibrosis. However, the expression of pSmad2/3 and p-eNOS was reduced in Sol-Eng(+) high mice. On the other hand, sEng and HFD did not significantly affect the expression of selected members of TGF beta signaling (membrane endoglin, TGF beta RII, ALK-5, ALK-1, Id-1, PAI-1), inflammation (VCAM-1, ICAM-1), oxidative stress (NQO1, HO-1) and heart remodeling (PDGF beta, COL1A1, beta-MHC). In conclusion, the results of this study confirmed that sEng, even combined with a high-fat diet inducing hypercholesterolemia administered for six months, does not affect the structure of the heart with respect to hypertrophy, fibrosis, inflammation and oxidative stress. Interestingly, pSmad2/3/p-eNOS signaling was reduced in both the heart in this study and the aorta in the previous study, suggesting a possible alteration of NO metabolism caused by six months exposure to high sEng levels and HFD. Thus, we might conclude that sEng combined with a high-fat diet might be related to the alteration of NO production due to altered pSmad2/3/p-eNOS signaling in the heart and aorta.
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
<a href="/cs/project/EF16_019%2F0000841" target="_blank" >EF16_019/0000841: Zvýšení účinnosti a bezpečnosti léčiv a nutraceutik: moderní metody - nové výzvy</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
PLoS One
ISSN
1932-6203
e-ISSN
—
Svazek periodika
15
Číslo periodika v rámci svazku
5
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
15
Strana od-do
e0233725
Kód UT WoS článku
000537552800152
EID výsledku v databázi Scopus
2-s2.0-85085854859