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

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

Increased levels of a soluble form of endoglin (sEng) circulating in plasma have been detected in various pathological conditions related to cardiovascular system. High concentration of sEng was also proposed to contribute to the development of endothelial dysfunction, but there is no direct evidence to support this hypothesis. Therefore, in the present work we analyzed whether high sEng levels induce endothelial dysfunction in aorta by using transgenic mice with high expression of human sEng. Transgenic mice with high expression of human sEng on CBAxC57Bl/6J background (Sol-Eng+) and age-matched transgenic littermates that do not develop high levels of human soluble endoglin (control animals in this study) on chow diet were used. As expected, male and female Sol-Eng+ transgenic mice showed higher levels of plasma concentrations of human sEng as well as increased blood arterial pressure, as compared to control animals. Functional analysis either in vivo or ex vivo in isolated aorta demonstrated that the endothelium-dependent vascular function was similar in Sol-Eng+ and control mice. In addition, Western blot analysis showed no differences between Sol-Eng+ and control mice in the protein expression levels of endoglin, endothelial NO-synthase (eNOS) and pro-inflammatory ICAM-1 and VCAM-1 from aorta. Our results demonstrate that high levels of soluble endoglin alone do not induce endothelial dysfunction in Sol-Eng+ mice. However, these data do not rule out the possibility that soluble endoglin might contribute to alteration of endothelial function in combination with other risk factors related to cardiovascular disorders.

• MeSH
• Aorta MeSH
• Arterial Pressure physiology   MeSH
• Vascular Cell Adhesion Molecule-1 metabolism   MeSH
• Endothelium, Vascular metabolism   pathology   MeSH
• Endoglin MeSH
• Intracellular Signaling Peptides and Proteins blood   MeSH
• Cardiovascular Diseases blood   metabolism   pathology   MeSH
• Intercellular Adhesion Molecule-1 metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Transgenic MeSH
• Mice MeSH
• Nitric Oxide Synthase Type III metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Vascular Cell Adhesion Molecule-1 MeSH
• Endoglin MeSH
• Eng protein, mouse MeSH Browser
• Intracellular Signaling Peptides and Proteins MeSH
• Intercellular Adhesion Molecule-1 MeSH
• Nos3 protein, mouse MeSH Browser
• Nitric Oxide Synthase Type III MeSH

C57BL/6J (B6) mice were demonstrated to be the most susceptible and C3H/HeJ (C3H) mice the most resistant to development of atherosclerosis. We hypothesized, whether pro-atherogenic (P-selectin, VCAM-1, and ICAM-1) and anti-atherogenic (endoglin and eNOS) proteins are expressed differently in aorta before the onset of atherosclerosis in these two mouse strains. B6 mice (n = 16) and C3H mice (n = 16) sustained on either chow or cholesterol (1 %) diet for 8 weeks. Biochemical analysis of lipoprotein profile and Western blot analysis of P-selectin, VCAM-1, ICAM-1, eNOS, endoglin, peNOS and TGF-βRII in aorta were performed. Western blot analysis revealed a lower expression of P-selectin by 7 %, VCAM-1 by 51 %, ICAM-1 by 6 %, and a higher expression of eNOS (by 18 %) in C3H mice in comparison with B6 mice after cholesterol diet. Further analysis revealed that cholesterol diet significantly increased the expression of endoglin (by 97 %), TGF-βRII (by 50 %), eNOS (by 21 %) and peNOS (by 122 %) in C3H mice, but not in B6 mice. We propose that lower expression of P-selectin, VCAM-1 and ICAM-1 and higher expression of eNOS in vivo in aorta of C3H mice might represent another potential mechanism for C3H mice being less susceptible to atherosclerosis when compared to B6 mice. In addition, endoglin seems to be involved in an upregulation of eNOS only in C3H mice. Thus, we propose that aorta of C3H mice is less prone to the expression of pro-inflammatory and endothelial dysfunction markers when compared to B6 mice, regardless of lipoprotein profile and before any signs of atherosclerotic process.

• MeSH
• Aorta enzymology   MeSH
• Atherosclerosis enzymology   genetics   prevention & control   MeSH
• Species Specificity MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Inflammation Mediators metabolism   MeSH
• Cell Adhesion Molecules metabolism   MeSH
• Mice, Inbred C3H MeSH
• Mice, Inbred C57BL MeSH
• Protective Factors MeSH
• Risk Factors MeSH
• Nitric Oxide Synthase Type III metabolism   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Inflammation Mediators MeSH
• Cell Adhesion Molecules MeSH
• Nos3 protein, mouse MeSH Browser
• Nitric Oxide Synthase Type III MeSH