Long term effects of soluble endoglin and mild hypercholesterolemia in mice hearts

• Published in: PloS one Vol. 15; no. 5; p. e0233725
• Main Authors: Vitverova, Barbora, Najmanova, Iveta, Vicen, Matej, Tripska, Katarina, Sa, Ivone Cristina Igreja, Hyspler, Radek, Pericacho, Miguel, Nachtigal, Petr
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.05.2020; Public Library of Science (PLoS)
• Subjects: Aorta; Biology and Life Sciences; Care and treatment; Cellular signal transduction; Cholesterol; Collagen (type I); Coronary vessels; Cytokines; Design of experiments; Development and progression; Diet; Endoglin; Experimental design; Exposure; Fibrosis; Gene expression; Genetic aspects; Glycoproteins; Health aspects; Heart; High fat diet; Hypercholesterolemia; Hypertension; Hypertrophy; Id1 protein; Inflammation; Intercellular adhesion molecule 1; Levels; Lipoproteins; Long term effects; Medicine and Health Sciences; Metabolism; Morphology; Myocardium; Oxidative stress; Pharmacy; Plasma; R&D; Research & development; Research and Analysis Methods; Signaling; Transgenic animals; Transgenic mice; Vascular cell adhesion molecule 1; Czech Republic; United States > US; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0233725

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, TGFβ 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 TGFβ signaling (membrane endoglin, TGFβRII, ALK-5, ALK-1, Id-1, PAI-1), inflammation (VCAM-1, ICAM-1), oxidative stress (NQO1, HO-1) and heart remodeling (PDGFβ, COL1A1, β-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.