Soluble endoglin and hypercholesterolemia aggravate endothelial and vessel wall dysfunction in mouse aorta
Language English Country Ireland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
29459262
DOI
10.1016/j.atherosclerosis.2018.02.008
PII: S0021-9150(18)30067-4
Knihovny.cz E-resources
- Keywords
- Endothelial dysfunction, Mice, Soluble endoglin, Vascular reactivity, eNOS,
- MeSH
- Aorta metabolism pathology physiopathology MeSH
- Atherosclerosis genetics metabolism pathology physiopathology MeSH
- Endothelium, Vascular metabolism pathology physiopathology MeSH
- Diet, High-Fat MeSH
- Endoglin genetics metabolism MeSH
- Phosphorylation MeSH
- Hypercholesterolemia complications etiology MeSH
- Humans MeSH
- Inflammation Mediators metabolism MeSH
- Disease Models, Animal MeSH
- Mice, Inbred C57BL MeSH
- Mice, Inbred CBA MeSH
- Mice, Transgenic MeSH
- Aortic Diseases genetics metabolism pathology physiopathology MeSH
- Smad2 Protein metabolism MeSH
- Smad3 Protein metabolism MeSH
- Signal Transduction MeSH
- Nitric Oxide Synthase Type III metabolism MeSH
- Up-Regulation MeSH
- Vasodilation MeSH
- Vasoconstriction MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Endoglin MeSH
- ENG protein, human MeSH Browser
- Inflammation Mediators MeSH
- Nos3 protein, mouse MeSH Browser
- Smad2 Protein MeSH
- Smad3 Protein MeSH
- Smad2 protein, mouse MeSH Browser
- Smad3 protein, mouse MeSH Browser
- Nitric Oxide Synthase Type 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
References provided by Crossref.org
High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice Aging
Long term effects of soluble endoglin and mild hypercholesterolemia in mice hearts
