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

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.

Companion diagnostic for the chloroquine use in the treatment of COVID-19: systems biology report of candidate markers.

“…Repurposing of their use for COVID-19 patients treated with chloroquine can be applied now. For example, a higher risk of adverse cardiac effects would be indicated by downregulation of albumin and up-regulation of amyloid precursor protein, tau protein, prion protein and soluble endoglin (21,22,26,43). Availability of data and material: All data are freely available.…”

TGF‐β superfamily co‐receptors in cancer

“…Whether there is a causative role for soluble endoglin on these pathologies continues to be investigated. Recent studies suggest a role for soluble endoglin in aortic endothelial dysfunction, but not in the alteration of heart structure 81,82 . Additionally, soluble endoglin induces increased arterial pressure, which may be due to a downstream increase in BMP4 expression 83 .…”

“…Recent studies suggest a role for soluble endoglin in aortic endothelial dysfunction, but not in the alteration of heart structure. 81,82 Additionally, soluble endoglin induces increased arterial pressure, which may be due to a downstream increase in BMP4 expression. 83 High soluble endoglin has been associated with metabolic disorders, including with cholesterol and bile acids, 84 and liver diseases, including liver cystic fibrosis, cirrhosis, and hepatocellular carcinoma.…”

Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities

“…Of note, expression levels and enzymatic activity of MMP-14 are increased in various conditions related to endothelial injury, activation, inflammation and senescence, as well as in pregnancy [ 17 , 18 , 19 , 20 , 21 ]. Several lines of evidence support a functional role of sEng in cardiovascular conditions and diseases, including endothelial dysfunction, anti-angiogenic activity, hypertension, increased vascular permeability, vascular remodeling, and inflammation-associated leukocyte adhesion and extravasation [ 8 , 14 , 20 , 22 , 23 , 24 , 25 , 26 , 27 ]…”