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Long term effects of soluble endoglin and mild hypercholesterolemia in mice hearts
Barbora Vitverova1, Iveta Najmanova1, Matej Vicen1
1Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
Insights
High soluble endoglin (sEng) levels combined with a high-fat diet did not alter heart structure in mice. However, this combination reduced specific signaling pathways (pSmad2/3/p-eNOS), potentially affecting nitric oxide metabolism.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Endocrinology
Background:
- Soluble endoglin (sEng) is implicated in cardiovascular pathologies.
- Previous studies linked high sEng and high-fat diet (HFD) to aortic endothelial dysfunction.
Purpose of the Study:
- To investigate the effects of high sEng and HFD on heart morphology, TGFβ signaling, inflammation, fibrosis, oxidative stress, and eNOS signaling in transgenic mice.
- To determine if sEng exacerbates HFD-induced cardiac changes.
Main Methods:
- Transgenic mice overexpressing human sEng (Sol-Eng+) were fed a HFD with cholesterol for six months.
- Cardiac morphology, gene expression (qRT-PCR), and protein levels (Western blot) were analyzed.
- Blood analysis was also performed.
Main Results:
- No significant effects of sEng and HFD on myocardial morphology, hypertrophy, or fibrosis were observed.
- Expression of pSmad2/3 and p-eNOS was reduced in mice with high sEng and HFD.
- Key markers for TGFβ signaling, inflammation, oxidative stress, and heart remodeling remained largely unaffected.
Conclusions:
- Combined exposure to high sEng and HFD for six months did not induce structural cardiac changes (hypertrophy, fibrosis, inflammation, oxidative stress).
- Reduced pSmad2/3/p-eNOS signaling suggests a potential alteration in nitric oxide (NO) metabolism.
- sEng and HFD may impact cardiac and aortic NO production through altered signaling pathways.
Abstract:
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.
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