Soluble endoglin and hypercholesterolemia aggravate endothelial and vessel wall dysfunction in mouse aorta
Jazyk angličtina Země Irsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
29459262
DOI
10.1016/j.atherosclerosis.2018.02.008
PII: S0021-9150(18)30067-4
Knihovny.cz E-zdroje
- Klíčová slova
- Endothelial dysfunction, Mice, Soluble endoglin, Vascular reactivity, eNOS,
- MeSH
- aorta metabolismus patologie patofyziologie MeSH
- ateroskleróza genetika metabolismus patologie patofyziologie MeSH
- cévní endotel metabolismus patologie patofyziologie MeSH
- dieta s vysokým obsahem tuků MeSH
- endoglin genetika metabolismus MeSH
- fosforylace MeSH
- hypercholesterolemie komplikace etiologie MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši inbrední CBA MeSH
- myši transgenní MeSH
- nemoci aorty genetika metabolismus patologie patofyziologie MeSH
- protein Smad2 metabolismus MeSH
- protein Smad3 metabolismus MeSH
- signální transdukce MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- upregulace MeSH
- vazodilatace MeSH
- vazokonstrikce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- endoglin MeSH
- ENG protein, human MeSH Prohlížeč
- mediátory zánětu MeSH
- Nos3 protein, mouse MeSH Prohlížeč
- protein Smad2 MeSH
- protein Smad3 MeSH
- Smad2 protein, mouse MeSH Prohlížeč
- Smad3 protein, mouse MeSH Prohlížeč
- synthasa oxidu dusnatého, typ III MeSH
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.
Center for Biological Research Spanish National Research Council 28040 Madrid Spain
Centrum for Research and Development University Hospital Hradec Kralove Czech Republic
Citace poskytuje Crossref.org
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