Acute manifestations of ischemic heart disease are among the most serious and fatal consequences of atherosclerotic processes. In this study, we hypothesized that a soluble proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble bone morphogenetic protein 4 (BMP-4), soluble E-selectin (sE-selectin), soluble endoglin (sENG) and soluble endocan (Endocan) would differ from healthy controls in myocardial infarction (MI) patients admitted to the hospital without any previous history of cardiovascular disease and with no cardioprotective drugs taken before admission. The study was conducted using a cross-sectional design. We analyzed data from 79 patients (mean age 54.1 ± 8.9, 18% of women) admitted for the first manifestation of MI and with no history of cardioprotective treatment use before the event. As a control group, we analyzed 17 age-matched healthy volunteers (mean age 51.5 ± 8.6, 47% of women). In addition to routinely obtaining clinical and laboratory data, we analyzed plasma concentrations of the aforementioned biomarkers using ELISA and Luminex analyses. Patients with MI did not differ from healthy controls in total cholesterol, LDL, non-HDL, and triglyceride levels. PCSK9, BMP-4, and sE-selectin levels did not differ significantly between the MI and the control group. Patients with MI had significantly higher sENG and Endocan levels than the control group. In addition, levels of sENG were significantly higher in patients with higher body mass index (BMI) and in smokers. We demonstrated that sENG could serve as a biomarker reflecting endothelial dysfunction in MI patients without prior treatment for cardiovascular risk factors.

• Keywords
• myocardial infarction, soluble endocan., soluble endoglin,
• MeSH
• Biomarkers blood   MeSH
• Endothelium, Vascular * physiopathology   pathology   metabolism   MeSH
• Adult MeSH
• E-Selectin blood   MeSH
• Endoglin * blood   MeSH
• Myocardial Infarction * blood   pathology   physiopathology   MeSH
• Bone Morphogenetic Protein 4 blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Proteins blood   MeSH
• Proprotein Convertase 9 blood   MeSH
• Proteoglycans blood   MeSH
• Cross-Sectional Studies MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Names of Substances
• Biomarkers MeSH
• BMP4 protein, human MeSH Browser
• E-Selectin MeSH
• Endoglin * MeSH
• ENG protein, human MeSH Browser
• ESM1 protein, human MeSH Browser
• Bone Morphogenetic Protein 4 MeSH
• Neoplasm Proteins MeSH
• PCSK9 protein, human MeSH Browser
• Proprotein Convertase 9 MeSH
• Proteoglycans MeSH
• SELE protein, human MeSH Browser

Age-related macular degeneration (AMD) is a progressive chronic disease causing visual impairment or central vision loss in the elderly. We hypothesized that successful rheopheresis would be associated with positive changes in soluble endoglin (sENG), PSCK9, alpha-2-macroglobulin (A2M), and hs-CRP levels. 31 elderly patients with the dry form of AMD, treated with rheopheresis with a follow-up period of at least 5 years and an average age of 68 ± 4 years, were evaluated. Each treated patient received a series of 8 procedures in 10 weeks and, after the 2-year period, another 2 procedures within 1 week. Then, the patients were followed up every 6 months and divided into the successfully treated and therapeutic failure group according to best-corrected visual acuity (BCVA), size of the drusen area, and the drusenoid pigment epithelium detachment (DPED). Based on the ophthalmological assessment, rheopheresis treatment was successful in 73% of AMD patients. The therapy was associated with a significant decrease in total cholesterol, LDL-C, HDL-C, apoprotein B, lipoprotein (a) levels, and rheologically important parameters, irrespective of the therapy's success or failure. The success of rheopheresis therapy was exclusively related to a significant decrease in sENG and A2M levels. Over the long term, rheopheresis prevented the decline of BCVA, reduced the DPED and area of macular drusen, and improved the preservation of an intact photoreceptor ellipsoid zone in most patients. Moreover, we showed for the first time that sENG and A2M could be potentially sensitive biomarkers of successful rheopheresis procedure, irrespective of lipid parameters changes.

• Keywords
• Age-related macular degeneration, Alpha-2-macroglobulin, Rheopheresis, Soluble endoglin,
• MeSH
• Biomarkers * blood   MeSH
• Endoglin * blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Macular Degeneration * therapy   blood   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Visual Acuity MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers * MeSH
• Endoglin * MeSH

BACKGROUND: C-reactive protein (CRP) is an acute inflammatory protein detected in obese patients with metabolic syndrome. Moreover, increased CRP levels have been linked with atherosclerotic disease, congestive heart failure, and ischemic heart disease, suggesting that it is not only a biomarker but also plays an active role in the pathophysiology of cardiovascular diseases. Since endothelial dysfunction plays an essential role in various cardiovascular pathologies and is characterized by increased expression of cell adhesion molecules and inflammatory markers, we aimed to detect specific markers of endothelial dysfunction, inflammation, and oxidative stress in spontaneously hypertensive rats (SHR) expressing human CRP. This model is genetically predisposed to the development of the metabolic syndrome. METHODS: Transgenic SHR male rats (SHR-CRP) and non-transgenic SHR (SHR) at the age of 8 months were used. Metabolic profile (including serum and tissue triglyceride (TAG), serum insulin concentrations, insulin-stimulated incorporation of glucose, and serum non-esterified fatty acids (NEFA) levels) was measured. In addition, human serum CRP, MCP-1 (monocyte chemoattractant protein-1), and adiponectin were evaluated by means of ELISA, histological analysis was used to study morphological changes in the aorta, and western blot analysis of aortic tissue was performed to detect expression of endothelial, inflammatory, and oxidative stress markers. RESULTS: The presence of human CRP was associated with significantly decreased insulin-stimulated glycogenesis in skeletal muscle, increased muscle and hepatic accumulation of TAG and decreased plasmatic cGMP concentrations, reduced adiponectin levels, and increased monocyte chemoattractant protein-1 (MCP-1) levels in the blood, suggesting pro-inflammatory and presence of multiple features of metabolic syndrome in SHR-CRP animals. Histological analysis of aortic sections did not reveal any visible morphological changes in animals from both SHR and SHR-CRP rats. Western blot analysis of the expression of proteins related to the proper function of endothelium demonstrated significant differences in the expression of p-eNOS/eNOS in the aorta, although endoglin (ENG) protein expression remained unaffected. In addition, the presence of human CRP in SHR in this study did not affect the expression of inflammatory markers, namely p-NFkB, P-selectin, and COX2 in the aorta. On the other hand, biomarkers related to oxidative stress, such as HO-1 and SOD3, were significantly changed, indicating the induction of oxidative stress. CONCLUSIONS: Our findings demonstrate that CRP alone cannot fully induce the expression of endothelial dysfunction biomarkers, suggesting other risk factors of cardiovascular disorders are necessary to be involved to induce endothelial dysfunction with CRP.

• Keywords
• Aorta, C-reactive protein, Endothelial dysfunction, Oxidative stress, Spontaneously hypertensive rat,
• MeSH
• Adiponectin MeSH
• Aorta MeSH
• Biomarkers metabolism   MeSH
• C-Reactive Protein metabolism   MeSH
• Chemokine CCL2 MeSH
• Hypertension * MeSH
• Insulins * metabolism   MeSH
• Rats MeSH
• Humans MeSH
• Metabolic Syndrome * diagnosis   genetics   MeSH
• Oxidative Stress MeSH
• Rats, Inbred SHR MeSH
• Inflammation MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adiponectin MeSH
• Biomarkers MeSH
• C-Reactive Protein MeSH
• Chemokine CCL2 MeSH
• CRP protein, human MeSH Browser
• Insulins * MeSH

Sepsis is a clinical syndrome characterized by a dysregulated response to infection. It represents a leading cause of mortality in ICU patients worldwide. Although sepsis is in the point of interest of research for several decades, its clinical management and patient survival are improving slowly. Monitoring of the biomarkers and their combinations could help in early diagnosis, estimation of prognosis and patient's stratification and response to the treatment. Circulating soluble endoglin (sEng) is the cleaved extracellular part of transmembrane glycoprotein endoglin. As a biomarker, sEng has been tested in several pathologic conditions where its elevation was associated with endothelial dysfunction. In this study we have tested the ability of sEng to predict mortality and its correlation with other clinical characteristics in the cohort of septic shock patients (n = 37) and patients with severe COVID-19 (n = 40). In patients with COVID-19 sEng did not predict mortality or correlate with markers of organ dysfunction. In contrast, in septic shock the level of sEng was significantly higher in patients with early mortality (p = 0.019; AUC = 0.801). Moreover, sEng levels correlated with signs of circulatory failure (required dose of noradrenalin and lactate levels; p = 0.002 and 0.016, respectively). The predominant clinical problem in patients with COVID-19 was ARDS, and although they often showed signs of other organ dysfunction, circulatory failure was exceptional. This potentially explains the difference between sEng levels in COVID-19 and septic shock. In conclusion, we have confirmed that sEng may reflect the extent of the circulatory failure in septic shock patients and thus could be potentially used for the early identification of patients with the highest degree of endothelial dysfunction who would benefit from endothelium-targeted individualized therapy.

• Keywords
• COVID-19, biomarker, endoglin, endothelial dysfunction, mortality, sepsis, shock,
• Publication type
• Journal Article MeSH

Membrane endoglin (Eng, CD105) is a transmembrane glycoprotein essential for the proper function of vascular endothelium. It might be cleaved by matrix metalloproteinases to form soluble endoglin (sEng), which is released into the circulation. Metabolic syndrome comprises conditions/symptoms that usually coincide (endothelial dysfunction, arterial hypertension, hyperglycemia, obesity-related insulin resistance, and hypercholesterolemia), and are considered risk factors for cardiometabolic disorders such as atherosclerosis, type II diabetes mellitus, and liver disorders. The purpose of this review is to highlight current knowledge about the role of Eng and sEng in the disorders mentioned above, in vivo and in vitro extent, where we can find a wide range of contradictory results. We propose that reduced Eng expression is a hallmark of endothelial dysfunction development in chronic pathologies related to metabolic syndrome. Eng expression is also essential for leukocyte transmigration and acute inflammation, suggesting that Eng is crucial for the regulation of endothelial function during the acute phase of vascular defense reaction to harmful conditions. sEng was shown to be a circulating biomarker of preeclampsia, and we propose that it might be a biomarker of metabolic syndrome-related symptoms and pathologies, including hypercholesterolemia, hyperglycemia, arterial hypertension, and diabetes mellitus as well, despite the fact that some contradictory findings have been reported. Besides, sEng can participate in the development of endothelial dysfunction and promote the development of arterial hypertension, suggesting that high levels of sEng promote metabolic syndrome symptoms and complications. Therefore, we suggest that the treatment of metabolic syndrome should take into account the importance of Eng in the endothelial function and levels of sEng as a biomarker and risk factor of related pathologies.

• Keywords
• Endoglin, Endothelial dysfunction, Hyperglycemia, Metabolic syndrome, Soluble endoglin,
• MeSH
• Atherosclerosis metabolism   pathology   MeSH
• Biomarkers metabolism   MeSH
• Cell Membrane metabolism   MeSH
• Diabetes Mellitus, Type 2 metabolism   pathology   MeSH
• Endoglin chemistry   metabolism   MeSH
• Gene Expression MeSH
• Cardiovascular Diseases metabolism   pathology   MeSH
• Humans MeSH
• Metabolic Syndrome metabolism   pathology   MeSH
• Nitric Oxide Synthase Type III metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Biomarkers MeSH
• Endoglin MeSH
• Nitric Oxide Synthase Type III MeSH

BACKGROUND: Lipoprotein apheresis (LA) is considered as an add-on therapy for patients with familial hypercholesterolemia (FH). We aimed to analyze the data collected in the last 15 years from FH patients treated with LA, to elucidate the benefit of this procedure with respect to plasma lipids, biomarkers of inflammation, and endothelial dysfunction and soluble endoglin. RESULTS: 14 patients (10 heterozygous FH patients (HeFH), 4 homozygous FH patients (HoFH)) were treated by long-term lipoprotein apheresis. Lipid levels were examined, and ELISA detected biomarkers of inflammation and soluble endoglin. Paired tests were used for intergroup comparisons, and a linear regression model served to estimate the influence of the number of days patients were treated with LA on the studied parameters. LA treatment was associated with a significant decrease of total cholesterol (TC), LDL-C, HDL-C, and apoB, in both HeFH and HoFH patients, after single apheresis and in a long-term period during the monitored interval of 15 years. Biomarkers of inflammation and endothelial dysfunction were reduced for soluble endoglin, hsCRP, and MCP-1, and sP-selectin after each procedure in some HeFH and HoFH patients. CONCLUSIONS: LA treatment up to 15 years, reduced cholesterol levels, levels of biomarkers related to endothelial dysfunction, and inflammation not only after each procedure but also in the long-term evaluation in FH patients. We propose that long-term LA treatment improves lipid profile and endothelial dysfunction in familial hypercholesterolemia patients, suggesting a promising improvement in cardiovascular prognosis in most FH patients.

• Keywords
• Familial hypercholesterolemia, Inflammation, Lipids, Lipoprotein apheresis, Soluble endoglin,
• MeSH
• Biomarkers MeSH
• Endoglin MeSH
• Hyperlipoproteinemia Type II * genetics   therapy   MeSH
• Humans MeSH
• Lipoproteins MeSH
• Blood Component Removal * MeSH
• Inflammation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• Endoglin MeSH
• Lipoproteins MeSH

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.

• MeSH
• Aorta metabolism   pathology   MeSH
• Diet, High-Fat adverse effects   MeSH
• Endoglin * blood   metabolism   MeSH
• Fibrosis MeSH
• Hypercholesterolemia metabolism   MeSH
• Hypertrophy MeSH
• Myocardium metabolism   pathology   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Transgenic MeSH
• Mice MeSH
• Nitric Oxide metabolism   MeSH
• Oxidative Stress MeSH
• Inflammation MeSH
• Animals MeSH
• Check Tag
• Mice 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
• Nitric Oxide MeSH

A soluble form of endoglin (sEng) released into the circulation was suggested to be a direct inducer of endothelial dysfunction, inflammation and contributed to the development of hypertension by interfering with TGF-β signaling in cardiovascular pathologies. In the present study, we assessed the hypothesis that high sEng level-induced hypertension via a possible sEng interference with TGF-β signaling pathways may result in inflammatory, structural or fibrotic changes in hearts of Sol-Eng+ mice (mice with high levels of soluble endoglin) fed either chow or high-fat diet. Female Sol-Eng+ mice and their age matched littermates with low plasma levels of sEng were fed either chow or high-fat diet (HFD). Heart samples were subsequently analyzed by histology, qRT-PCR and Western blot analysis. In this study, no differences in myocardial morphology/hypertrophy and possible fibrotic changes between Sol-Eng+ mice and control mice were detected on both chow and HFD. The presence of sEng did not significantly affect the expression of selected members of TGF-β signaling (membrane endoglin, TGFβRII, ALK-5, ALK-1, Id-1, PAI-1 and activated Smad proteins-pSmad 1,5 and pSmad 2,3), inflammation, heart remodeling (PDGFb, Col1A1) and endothelial dysfunction (VCAM-1, ICAM-1) in the hearts of Sol-Eng+ mice compared to control mice on both chow and high-fat diet. High levels of soluble endoglin did not affect microscopic structure (profibrotic and degenerative cardiomyocyte changes), and specific parts of TGF-β signaling, endothelial function and inflammation in the heart of Sol-Eng+ mice fed both chow diet or HFD. However, we cannot rule out a possibility that a long-term chronic exposure (9 months and more) to soluble endoglin alone or combined with other cardiovascular risk factors may contribute to alterations of heart function and structure in Sol-Eng+ mice, which is the topic in our lab in ongoing experiments.

• Keywords
• Heart, Inflammation, Mice, Soluble endoglin, TGF-β signaling,
• MeSH
• Endoglin biosynthesis   genetics   MeSH
• Hypertension blood   complications   MeSH
• Cardiomyopathy, Hypertrophic blood   etiology   pathology   MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Disease Models, Animal MeSH
• Myocardium metabolism   pathology   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Transgenic MeSH
• Mice MeSH
• Oxidative Stress MeSH
• Gene Expression Regulation * MeSH
• RNA genetics   MeSH
• Signal Transduction MeSH
• Heart MeSH
• Gene Expression Profiling MeSH
• Transforming Growth Factor beta genetics   metabolism   MeSH
• Blotting, Western MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Endoglin MeSH
• Eng protein, mouse MeSH Browser
• RNA MeSH
• Transforming Growth Factor beta MeSH