dcyphr | Circulating soluble endoglin modifies the inflammatory response in mice


Patients with cardiovascular disease and inflammation have high levels of soluble endoglin in their blood. Mice expressing human soluble endoglin (sEng+) were put under different inflammatory conditions. sEng+ mice has reduced lung and kidney injury after inflammation. There were also lower levels of neutrophils in inflamed lungs and kidneys. The sEng+ mice also had less proinflammatory cytokines, like TNF-alpha, IL1-beta, and IL6 compared to the wildtype mice. Cell adhesion molecules like ICAM-1 and VCAM-1 were also reduced in the sEng+ mice. This study shows us that soluble endoglin regulated inflammation, and is a possible treatment for inflammatory diseases.


The aim of this study is to find the effect of soluble endoglin on inflammation.


Dysregulation of inflammation causes many diseases throughout the entire body, and can be fatal. Current anti-inflammatory medications, like NSAIDs and steroids, do not target inflammation well enough and have side effects. Endoglin is just one possible target to treat inflammation. Membrane bound endoglin is usually attached to the membrane of endothelial cells, but can be cleaved into soluble endoglin, where it is free to go into the body’s circulation. High serum levels of soluble endoglin can predict a heart attack, heart failure, coronary artery disease, hypertension, and preeclampsia. Some studies suggest that soluble endoglin can outcompete membrane bound endoglin, therefore decreasing the function of the membrane bound endoglin. For example, soluble endoglin can bind to TGF-beta before membrane bound endoglin is able to, so TGF-beta can no longer communicate with the endothelial cells. In this study, multiple inflammatory conditions are given to mice containing the human sEng+ gene. This allows us to see the effect of soluble human endoglin on inflammation.


Acute lung injury (ALI) is a fatal condition where the lungs become fluid filled and fail to breathe. LPS was used to induce ALI in both normal and sEng+ mice. The levels of neutrophils were decreased in the sEng+ mice compared to the normal mice. sEng+ did reduce lung injury in many cases, but this difference was not significant. In the kidney inflammation condition, the neutrophils were also interestingly decreased in sEng+ mice. The level of kidney damage was significantly decreased in the sEng+ mice.

In the carrageenan air pouch test, the level of white blood cells were decreased compared to the normal mice condition. Myeloperoxidase (MPO) is released by some white blood cells during inflammation. sEng+ mice had significantly reduced MPO levels in the damaged kidney compared to the normal mice with kidney damage.

The research team also looked for the effect of sEng on proinflammatory cytokines. The usually cytokines we see in response to inflammation are TNF-alpha, IL1-beta, and IL6. Overall, sEng+ tended to reduce TNF-alpha, IL1-beta, IL6, but not enough to be considered statistically significant.

To see if the vessels of the lungs were leaking, the protein concentration was tested. The sEng+ decreased the protein concentration, showing that the vessels were less leaky. sEng+ mice also had less edema than normal mice.

Under inflammatory conditions, the creased cytokines cause expression of adhesion molecules like ICAM-1 and VCAM-1 to increase. The sEng+ mice had lower levels of ICAM-1 and VCAM-1 than the normal mice under inflammatory conditions.


Inflammation causes so many severe diseases and complications of diseases that would otherwise be less severe. For example, inflammation can cause diabetic patients to have heart attacks, strokes, and kidney disease. Strangely, many patients with diseases caused by inflammation have high levels of sEng in their circulation. This causes sEng to stand out as a flag for inflammation, but it is still unknown exactly why we see sEng along with inflammation.

This study showed that untreated sEng+ mice do not have fatal side effects, but that they actually seem to protect against inflammation. The thought behind sEng is that it acts to antagonize- or work against- its membrane bound form. This would prevent the membrane bound endoglin from interacting with TGF-beta, and reducing some complications from inflammation. In this study, it is also shown that endoglin, in its membrane bound and soluble form, may work together to regulate the movement of white blood cells through the vessels and into the target tissue. Just like we see with the TGF-beta example, sEng may decrease the ability of membrane bound endoglin to transport white blood cells across the membrane by out competing it. It should be noted that this is just a hypothesis with some supporting data, but has not been proven yet.

This study did prove that vascular permeability after inflammation was reduced by sEng for the first time. We also see here the protective effects of sEng against cell adhesion molecules. All of the findings of this study add interesting perspective into sEng’s role in the inflammatory response. This allows us to better understand disease caused by inflammation and better create treatments for these diseases.


This study used lipopolysaccharide (LPS) and carrageenan air pouches to induce inflammation and injury in the lungs. Ischemia was surgically induced to create kidney injury. Light microscopy was used to analyze the tissue samples. Protein concentration in the air pouches was determined using absorbance. Lung tissue was weighed to determine edema. FITC-Dextran intravenous injection was used to measure the vascular permeability of the lungs. ELISA, PCR, and western blot were also used to determine levels of endoglin throughout the samples.


More research should be done to confirm the hypothesis of sEng on membrane bound endoglin and inflammation. Still, this research gives us insight on sEng, inflammation, and possible treatments of inflammatory diseases.