Expression of endoglin, CD105, in conjunctival melanocytic nevi: Is it suspicious like in thyroidology? Oculi plus vident quam oculus?

SUMMARY Objective: The aim of this study was to evaluate the expression of endoglin and its correlation with histopathological and clinical findings in conjunctival nevi. Methods: The study included archival formalin-fixed, paraffin-embedded tissue sections of 44 patients with conjunctival nevi. Immunohistochemical staining for CD105 had been performed with monoclonal mouse antihuman CD105 antibodies. The intratumoral microvessel density for quantification of tumoral vascularization had been determined by this marker. Results: The expression of CD105 was positive in 30 (68.2%) cases. There was a statistically significant difference in the level of CD105 expression regarding the histological type of nevus (p=0.03) and intralesional cysts status (p=0.02). Spearman's rho (ρ −0.316) revealed a significant negative correlation between the expression of endoglin and the histological type of nevus (p=0.03) and between the expression of endoglin and the presence of intralesional cysts (ρ −0.380, p=0.01). Conclusion: This study suggests that endoglin could be a useful diagnostic and prognostic marker in differentiating between benign and malignant melanocytic ocular lesions.

Telangiectasia hemorrágica hereditaria durante el embarazo: Reporte de caso / Hereditary hemorrhagic telangiectasia during pregnancy: Case report

Resumen ANTECEDENTES: La telangiectasia hemorrágica hereditaria, o síndrome de Rendu-Osler-Weber, es una enfermedad vascular, hereditaria y autosómica caracterizada por telangiectasias mucocutáneas y malformaciones arteriovenosas en el pulmón, el cerebro e hígado. La prevalencia estimada es de 1.5 a 2 personas afectadas por cada 10,000 habitantes. El 90% de los casos se debe a una mutación en el gen endoglina y en el de la cinasa 1 similar al receptor de activina (ACVRL1). En la mujer embarazada, la telangiectasia hemorrágica hereditaria es de alto riesgo, sobre todo durante el segundo y tercer trimestre. OBJETIVO: Reportar un caso de telangiectasia hemorrágica hereditaria y exponer las complicaciones que pueden registrarse durante el embarazo. CASO CLÍNICO: Paciente de 23 años, con antecedente heredofamiliar de madre con diagnóstico de telangiectasia hemorrágica hereditaria (síndrome de Osler-Weber-Rendu) que falleció a los 38 años. Antecedente personal patológico de telangiectasia hemorrágica hereditaria, con diagnóstico a los 12 años luego de múltiples episodios de epistaxis. Recibió tratamiento con transfusiones sanguíneas en múltiples ocasiones y 200 mg de sulfato ferroso cada 24 horas. CONCLUSIÓN: La telangiectasia hemorrágica hereditaria condiciona, en la mujer embarazada, la aparición de complicaciones que pueden poner en riesgo la vida de la madre y el feto. Las mujeres con antecedente conocido deben valorarse antes de la concepción con el propósito de conocer el estado de la enfermedad.

Abstract BACKGROUND: Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber syndrome, is an autosomal inherited vascular disease characterized by mucocutaneous telangiectasias and arteriovenous malformations in the lung, brain and liver. The estimated prevalence is 1.5 to 2 affected persons per 10,000 population. Ninety percent of cases are due to a mutation in the endoglin gene and in the activin receptor-like kinase 1 gene (ACVRL1). In pregnant women, hereditary hemorrhagic telangiectasia is high risk, especially during the second and third trimester. OBJECTIVE: To report a case of hereditary hemorrhagic telangiectasia and to expose the complications that can occur during pregnancy. CLINICAL CASE: 23-year-old patient, with hereditary family history of mother diagnosed with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) who died at 38 years of age. Personal pathological history of hereditary hemorrhagic telangiectasia, diagnosed at the age of 12 years after multiple episodes of epistaxis. She was treated with multiple blood transfusions and 200 mg of ferrous sulfate every 24 hours. CONCLUSION: Hereditary hemorrhagic telangiectasia conditions, in pregnant women, the appearance of complications that can put the life of the mother and fetus at risk. Women with a known history should be evaluated before conception in order to know the status of the disease.

Generation of αGal-enhanced bifunctional tumor vaccine

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END+/Gal+-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.

Regulatory Mechanism and Function of Endoglin in Angiogenesis / 中国生物化学与分子生物学报

The formation of new blood vessels and homeostasis are important to ensure the normal physiological activities of cells. The blood vessel formation is strictly regulated by many factors for the stabilities and functions of internal environment and immune systems. Endoglin (ENG), a type I transmembrane glycoprotein mainly expressed on endothelial cells, plays an important role in angiogenesis and homeostasis by acting as a co⁃receptor of transforming growth factor β family. With more and more proteins interacting with ENG have been uncovered, such as matrix metalloproteinase 14 (MMP14), integrin, leucine⁃rich alpha⁃2⁃glycoprotein⁃1 (LRG1) and GAIP interacting protein C⁃terminus (GIPC), many new research progresses in molecular mechanism of ENG have been developing recently. However, the exquisite regulatory network between these proteins remains to be explored and combed. Understanding the characteristics of these proteins, their influences in signal transduction and their contribution to angiogenesis under patho⁃physiological conditions will be helpful for the development of novel therapeutics. This review summarized the interactions between ENG and TGF⁃β or non⁃TGF⁃β family associated proteins in regulating angiogenesis. We also proposed some suggestions for future study on ENG allowing us to better understand the mechanisms of ENG⁃associated diseases.

CD105 as a tool for assessing microvessel density in renal cell carcinoma

Background: Angiogenesis plays an essential role in both tumor growth and metastasis. CD105 expression was correlated with prognosis in many tumors, but its value in renal cell carcinoma (RCC) is still questionable. Materials and Methods: The aim of this study was to evaluate microvessel density (MVD) by using CD105 marker, in 95 cases of renal cell carcinoma. Results: CD105 showed positivity in 93 cases. The mean MVD value was significantly higher in clear cell carcinoma compared to papillary and chromophobe subtypes (P = 0.000). We noticed a significant correlation between MVD and ISUP grade (P = 0.007). The highest MVD value was observed in tumors with ISUP grade 1 and 2, while the lowest MVD value was noted in ISUP grade 3 tumors. A high vessel density was identified in tumors with a low Fuhrman grade, compared to those with a high grade (P = 0.010). MVD value was lower in tumors with a larger diameter, compared to small ones (P = 0.026). Conclusion: In conclusion, CD105 expression (MVD) is inversely related to tumor aggressiveness in clear cell RCC and can be used as a favorable prognosis marker. The vascularity differences between histological subtypes of RCCs could be useful for a better selection of patients that may benefit from anti-angiogenic therapies.

The prognostic and predictive significance of plasma type 1 plasminogen activator inhibitor and endoglin in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy

Aim: This study aims to evaluate the prognostic and predictive value of plasma plasminogen activator inhibitor-1 (PAI-1) and endoglin in metastatic colorectal cancer (mCRC) patients receiving chemotherapy with bevacizumab. Materials and Methods: Between April 2012 and September 2013, 47 mCRC patients with a mean age of 58.5 ± 9.6 years were included in the study. Male-to-female ratio was 29/18. The baseline and posttreatment plasma PAI-1 and serum endoglin levels after 3 cycles of bevacizumab-containing chemotherapy were evaluated. The percent change between baseline and posttreatment levels after treatment was also recorded. Results: The median follow-up duration was 26.6 months (range 1.8–70.2 months). The clinical benefit rate was 70% (partial response [32%], stable disease [38%]). Overall survival was 20.8 ± 1.5 months. The patients with progressive disease had statistically significantly higher baseline PAI-1 level (57.9 pg/mL vs. 29.9 pg/mL, P = 0.036). The percent change of the plasma PAI-1 level after the third cycle of treatment was also statistically significantly lower in those with clinical benefit (P = 0.035). However, there was no statistically significant difference in endoglin level and its change after therapy with respect to the response to treatment (P = 0.771 and P = 0.776, respectively). Plasma PAI-1 level had no statistically significant effect on survival (P = 0.709). Conclusion: Baseline plasma PAI-1 level and its percent change with bevacizumab were shown to have statistically significant predictive value for the response to therapy whereas serum endoglin had no statistically significant predictive value for the response to therapy. However, neither PAI-1 nor endoglin had prognostic significance in mCRC

Spectrum of Novel Hereditary Hemorrhagic Telangiectasia Variants in an Austrian Patient Cohort

OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disorder characterized by pathogenic blood vessel development and maintenance. HHT type 1 (HHT1) and type 2 (HHT2) are caused by variants in endoglin (ENG) and activin receptor-like kinase-1 (ACVRL1), respectively. The aim of this study was to identify the spectrum of pathogenic variants in ENG and ACVRL1 in Austrian HHT families. METHODS: In this prospective study, eight Austrian HHT families were screened for variants in ENG and ACVRL1 by polymerase chain reaction amplification and sequencing of DNA isolated from peripheral blood. RESULTS: Heterozygous variants were identified in all families under study. HHT1 was caused by a novel c.816+1G>A splice donor variant, a novel c.1479C>A nonsense (p.Cys493X) variant and a published c.1306C>T nonsense (p.Gln436X) variant in ENG. Variants found in ACVRL1 were novel c.200G>C (p.Arg67Pro) and known c.772G>A (p.Gly258Ser) missense variants in highly conserved residues, a known heterozygous c.100dupT frameshift (p.Cys34Leufs*4) and the known c.1204G>A missense (p.Gly402Ser) and c.1435C>T nonsense (p.Arg479X) variants as causes of HHT2. CONCLUSION: Novel and published variants in ENG (37.5%) and ACVRL1 (62.5%) were exclusively identified as the cause of HHT in an Austrian patient cohort. Identification of novel causative genetics variants should facilitate the development of tailored therapeutical applications in the future treatment of autosomal dominant HHT.

Anti-tumor activity of a recombinant endoglin-MIP3α Fc-fusion protein in mice with hepatocellular carcinoma

Objective: To investigate the effects of a recombinant endoglin-macrophage inflammatory protein 3α Fc-fusion protein (EM) vaccine on tumor angiogenesis and growth in mice with H22 hepatocellular carcinoma. Methods: An in vivo hepatoma mouse model was established. Seven days after subcutaneous inoculation of H22 tumor cells, mice were randomly divided into four groups: EM, endoglin Fc-fusion protein, macrophage inflammatory protein 3α Fc-fusion protein, and normal saline groups. Tumor volume and survival rate of mice were studied at 3-day intervals. Microvessel density of the tumors and tumor cell proliferation were detected by immunohistochemistry, and tumor cell apoptosis was detected by TdT-mediated biotinylated-dUTP nick-end label staining. The number of CD11c and CD86 positive dendritic cells were detected by flow cytometry. Results: Compared with the other groups, the tumor volume became smaller, and the survival time was longer in the EM-treated group. Besides, microvessel density and cell proliferation index were significantly lower, while the tumor cell apoptosis index was significantly higher in the EM-treated group. Besides the number of CD11c and CD86 positive dendritic cells in EM-treated mice was larger than that in other groups. Conclusions: EM Fc-fusion protein could effectively inhibit tumor growth through inhibiting endoglin-related tumor angiogenesis and cell proliferation, promoting tumor cell apoptosis, and could induce a certain degree of antitumor immune responses.

Progress in the study for pathogenesis and clinical treatment of preeclampsia / 解放军医学杂志

Preeclampsia (PE) is a serious complications during pregnancy, with a global incidence of 2%–8%. It is one of the important causes of the incidence and death of pregnant women and parturients. The main clinical manifestations are hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg), proteinuria (>0.3 g/24 h) can be accompanied by renal dysfunction, thrombocytopenia, liver dysfunction, pulmonary edema and other multi-system and multiple organ involvement. Antiphospholipid antibody syndrome, hypertension, diabetes, chronic kidney disease, obesity, PE family history, multiple pregnancy, maternal old age are the risk factors of PE. At present, the pathogenesis of PE is not completely clear, but more and more evidences suggest that the abnormal level of angiogenic factors and coagulation dysfunction are the main causes of the disease. The research progress in recent years has been reviewed in present paper in the pathogenesis and clinical treatment of PE, so as to provide a reference for clinical use.

Anti-tumor activity of a recombinant endoglin-MIP3α Fc-fusion protein in mice with hepatocellular carcinoma

Objective: To investigate the effects of a recombinant endoglin-macrophage inflammatory protein 3α Fc-fusion protein (EM) vaccine on tumor angiogenesis and growth in mice with H22 hepatocellular carcinoma. Methods: An in vivo hepatoma mouse model was established. Seven days after subcutaneous inoculation of H22 tumor cells, mice were randomly divided into four groups: EM, endoglin Fc-fusion protein, macrophage inflammatory protein 3α Fc-fusion protein, and normal saline groups. Tumor volume and survival rate of mice were studied at 3-day intervals. Microvessel density of the tumors and tumor cell proliferation were detected by immunohistochemistry, and tumor cell apoptosis was detected by TdT-mediated biotinylated-dUTP nick-end label staining. The number of CD11c and CD86 positive dendritic cells were detected by flow cytometry. Results: Compared with the other groups, the tumor volume became smaller, and the survival time was longer in the EM-treated group. Besides, microvessel density and cell proliferation index were significantly lower, while the tumor cell apoptosis index was significantly higher in the EM-treated group. Besides the number of CD11c and CD86 positive dendritic cells in EM-treated mice was larger than that in other groups. Conclusions: EM Fc-fusion protein could effectively inhibit tumor growth through inhibiting endoglin-related tumor angiogenesis and cell proliferation, promoting tumor cell apoptosis, and could induce a certain degree of antitumor immune responses.

Descrição da frequência de variantes genéticas no gene da endoglina em uma população do Nordeste do Brasil / Description of the frequency of genetic variants in the endoglin gene in a population of Northeast Brazil

Introdução: a endoglina (ENG, CD105) é um co-receptor da família transforming growth factor-beta e participa da regulação de processos celulares como proliferação, diferenciação, migração e apoptose. ENG é mais conhecida por sua expressão em células endoteliais, desempenhando papel importante na angiogênese e vasculogênese, porém sua expressão já foi associada a diferentes desfechos patogênicos, inclusive devido a mutações no gene ENG. Objetivos: descrever a frequência de variantes genéticas no gene ENG, comparar com populações ancestrais e analisar as variantes genéticas que possam estar envolvidas em processos patogênicos em outras populações. Metodologia: foi utilizado o banco de dados do programa SCAALA (Social Change Asthma and Allergy in Latin America) para a população do estudo, sendo genotipado 1309 indivíduos usando o chip Illumina 2.5 Human Omni Bead e feitas análises in silico utilizando plataformas on-line. Resultados: as variantes genéticas rs10987746, rs10121110, rs11792480 e rs16930129 apresentaram frequência de menor alelo entre 16 a 48% na população estudada, as quais foram mais reiteradamente próximas do padrão africano que do europeu. Os SNVs foram relacionados aos mecanismos regulatórios genéticos conhecidos, pressupondo que essas variantes não estejam envolvidas diretamente em processos funcionais. Conclusão: são necessárias maiores investigações referentes aos mecanismos funcionais deste gene, visto que a endoglina participa de uma gama de processos celulares importantes e mais esforços devem ser feitos para estudos genéticos na população brasileira, considerando a mistura de populações.

Introduction: the endoglin (ENG, CD105) is a coreceptor of the family transforming growth factor-beta and participates in the regulation of cellular processes such as proliferation, differentiation, migration and apoptosis. ENG She is best known for your expression in endothelial cells, playing an important role in angiogenesis and vasculogenesis, but its expression has already been associated with different pathogenic outcomes, including due to mutations in the ENG gene. Objectives: describe the frequency of genetic variants in the ENG gene in the population of northeastern Brazil, compare with ancestral populations and analyze genetic variants that may be involved in pathogenic processes in other populations. Methodology: we used the SCAALA program database (Social Change Asthma and Allergy in Latin America) for the population of the study, and the DNA of 1309 individuals were genotyped using the Illumina chip 2.5 Human Omni Bead and made in silico analysis. Results: the SNVs rs10987746, rs10121110, rs11792480 and rs16930129 presented lower allele frequency between 16 to 48% in the population studied, which were more consistently next African European standard. The SNVs were related to known genetic regulatory mechanisms assuming that these variants are not directly involved in functional processes. Conclusion: further investigation regarding the functional mechanisms of this gene are necessary, since the endoglin participates in a range of important cellular processes and more efforts should be made for genetic studies in the Brazilian population, considering the mixture of populations.

Clinical and genetic diagnosis in a hereditary hemorrhagic telangiectasia family / 中南大学学报(医学版)

Objective:To investigate the clinical features and feasibility genetic diagnosis in a hereditary hemorrhagic telangiectasia (HHT) family,and to explore the application of gene mutation testing in HHT diagnosis.Methods:Medical histories and clinical features of a family were analyzed to diagnose HHT patients and suspected individuals according to the clinical diagnostic criteria.Sequence analysis of endoglin (ENG) and activin A receptor like type 1 (ACVRL1) gene in the proband was performed with PCR and Sanger sequencing technology.After the possible pathogenic mutation was identified in the proband,the specific mutation was detected in the suspected individuals and part of other family members.Then the genetic diagnoses were concluded.Results:There were 5 family members in 4 generations manifested with epistaxis.According to the clinical diagnosis criteria,the proband with epistaxis,mucocutaneous telangiectases,visceral arteriovenous malformation and family history was diagnosed as HHT;while 2 survival family members with epistaxis and family history were suspected individuals.A substitution mutation in the 5'-untranslated region(5'-UTR) of ENG c.1-127 C＞T was detected in the proband and the 2 suspected individuals,which did not exist in other family members.Based on the clinical and genetic findings,the 2 clinically suspected individuals were diagnosed as HHT.Conclusion:There is great variability of the clinical manifestations among HHT patients.ENG c.1127 C＞T mutation is the possible pathogenic variant of the HHT family.A combination of clinical and genetic diagnosis could improve the diagnosis and treatment of HHT.

Significancia del desbalance de los factores angiogénicos en preeclampsia

La participación de los factores antiangiogénicos, la forma soluble de la fms-semejante a la tirosina quinasa (Flt-1s) y la endoglina soluble (Engs), en el desarrollo de la preeclampsia (PE) se ha demostrado en múltiples estudios clínicos y experimentales. Estos estudios están complementados por estudios en animales, en los cuales la sobreexpresión de estos factores antiangiogénicos origina manifestaciones clínicas muy similares a la PE. El origen de esta enfermedad permanece desconocido. Sin embargo, factores genéticos, ambientales e inmunológicos parecen alterar el desarrollo normal de la placenta, lo cual conduce últimamente a la PE. Flt-1s y Engs inhiben la producción y las propiedades proangiogénicas del factor de crecimiento vascular endotelial (FCVE) y del factor de crecimiento placentario (FCP), necesarios para el desarrollo normal vascular de la placenta y las adaptaciones vasculares fisiológicas del embarazo. Cantidades exageradas de Flt-1s y Engs se producen en la placenta disfuncional y se liberan en la circulación materna. Altas concentraciones de Flt-1s y Engs se encuentran en la circulación materna semanas antes de que la enfermedad sea detectada clínicamente. Las capacidades de los factores angiogénicos para predecir PE en embarazos asintomáticos de riesgo bajo y alto son inconsistentes y no útiles para el uso clínico. Por otro lado, proporciones de los factores Flt-1s/FCP, FCP/Flt-1s, y FCP/Eng poseen valores predictivos más altos para diagnosticar PE y predecir sus complicaciones en mujeres con sintomatología de PE. En estas condiciones, el uso clínico de estos marcadores biológicos podría ser implementado en un futuro cercano. Las propiedades biológicas y farmacocinéticas de las estatinas las convierten en uno de los medicamentos con más potencial preventivo para la PE. Otros opciones terapéuticas que se están estudiando son medicamentos que directamente inhiban los factores antiangiogénicos circulantes. Estudios in vitro y estudios pilotos clínicos se están realizando actualmente examinando la seguridad materno-fetal, la transferencia placentaria y la efectividad de estas terapias.

The role of the antiangiogenic factors, the soluble form of the fms-like tyrosine kinase receptor 1 (sFlt1) and the soluble endoglin (sEng), in the development of preeclampsia (PE) has been demonstrated in multiple clinical and experimental studies. These studies are complemented by animal studies, in which overexpression of these antiangiogenic factors leads to clinical manifestations similar to PE. Although, the origin of this disease remains unknown, genetic, environmental, and immunological factors appear to affect the normal placental development, resulting ultimately in PE. sFlt-1 and sEng inhibit the proangiogenic properties of the vascular endothelial growth factor (VEGF) and the placental growth factor (PlGF), affecting the normal vascular development in the placenta and the physiological vascular adaptations that occur in pregnancy. Exaggerated amounts of sFlt-1 and sEng, produced in the dysfunctional placenta, are released into the maternal circulation and elevated circulating concentrations of these antiangiogenic factors are found several weeks prior to the clinical manifestations of the disease. Multiple studies have reported the capacity of circulating antiangiogenic factor concentrations to predict PE in asymptomatic low and high risk pregnancies. The reported predictive values of sFlt-1 and sEng are inconsistent across these studies and therefore their clinical use in this population is not recommended. On the other hand, maternal plasma concentrations of these factors appear to have a better performance in women with symptoms of PE. Among the possible combinations, the ratios of sFlt-1/PlGF, PlGF/sFlt-1, and PlGF/Engs seem to have the highest sensitivities and specificities to diagnose PE as well as the highest predictive values for PE-related adverse outcomes. These properties support their clinical use in this setting and it is likely those ancillary tests will be incorporated to the clinical practice in the near future. The participation of antiangiogenic factors in the pathogenesis of PE, also have stimulated investigation of new targeted therapies. The biological and pharmacokinetic properties of statins have converted them in one of the most promising preventive therapies for this disease. Others are investigating agents that directly inhibit the circulating antiangiogenic factors. In-vitro and pilot clinical studies are currently evaluating the effectiveness, maternal-fetal safety, and placental transference of these therapies.

Clinical efficacy of human blood albumin and small dose heparin in treatment of severe preeclampsia and their effect on Endoglin,VEGF and Flt-1 expression in placenta tissues / 中国生化药物杂志

Objective To study the clinical efficacy of human blood albumin and small dose heparin in treatment of severe preeclampsia and its effect on the expression of Endoglin,vascular endothelial growth factor (VEGF)and its receptors (Flt)in placental tissue.Methods 60 cases of severe preeclampsia collected in weifang yidu central hospital from October 2012 to January 2014 were randomly divided into experimental group and control group,each had 30 cases.Control group were given oral antihypertensive,expansion and diuretic treatment.Experiment group were received injection with 500 mL 5% glucose,60 mL 25% magnesium sulfate and 25 mg heparin on the basis of control group,one time each day,for successive seven days.Another 30 cases of normal full-term pregnancy for cesarean section delivery collected in our hospital during the same period were as blank group.Mean arterial pressure (Kpa)and 24 h urine protein quantitative and clinical efficacy were observed and compared between experimental group and control group before and after treatment.curative effect. Microscopically observed treatment after Endoglin in blank group, control group and experimental group placenta tissue,The expression of Endoglin,VEGF and Flt 1 in placental tissue among three groups were observed by microscope, and their positive expression rate were compared. Results The mean arterial pressure and urine protein were all improved after treatment in control group,and experimental group,but the latter was more obvious than the former(P<0.05 ).The expression location of Endoglin,VEGF and PLT-1 in three groups were the same with microscopic observation.Compared with blank group,the positive expression rate of Endoglin,VEGF protein and PLT-1 in placenta of other two groups were higher(P<0.05),and those in experimental group were more higher than control group(P<0.05).Conclusion Human blood albu min and small dose heparin can effectively improve the indexes of quantitative Kpa and 24 h urine protein in severe preeclampsia, reduce the expression of Endoglin,VEGF and Flt 1 protein in placental tissue.

Contrasting Roles of Different Endoglin Forms in Atherosclerosis

Endoglin (also known as CD105 or TGF-beta type III receptor) is a co-receptor involved in TGF-beta signaling. In atherosclerosis, TGF-beta signaling is crucial in regulating disease progression owing to its anti-inflammatory effects as well as its inhibitory effects on smooth muscle cell proliferation and migration. Endoglin is a regulator of TGF-beta signaling, but its role in atherosclerosis has yet to be defined. This review focuses on the roles of the various forms of endoglin in atherosclerosis. The expression of the two isoforms of endoglin (long-form and short-form) is increased in atherosclerotic lesions, and the expression of the soluble forms of endoglin is upregulated in sera of patients with hypercholesterolemia and atherosclerosis. Interestingly, long-form endoglin shows an atheroprotective effect via the induction of eNOS expression, while short-form and soluble endoglin enhance atherogenesis by inhibiting eNOS expression and TGF-beta signaling. This review summarizes evidence suggesting that the different forms of endoglin have distinct roles in atherosclerosis.

Endoglin concentration in peritoneal fluid of patients with endometriosis.

Background: Endoglin is a specific angiogenic factor suspected to involve in the pathogenesis of endometriosis. The aim of this study was to evaluate the significance of endoglin concentration in the peritoneal fluid of patients with endometriosis. Methods: This pilot study was performed between March 2011 and July 2012 at Dr. Wahidin Sudirohusodo Hospital and another private hospital in Makassar, Indonesia. This was an observational, cross-sectional study. All patients undergoing laparoscopy for infertility and other cases with suitable inclusion criteria were asked to answer a questionnaire and had a 5 cc peritoneal fluid sample taken for measurement of peritoneal endoglin concentration using ELISA. Endometriosis stage was classified using ASRM criteria and divided into two groups, mild and severe. All data were analyed using Excel and Spearman correlation analysis. Results: In the endometriosis group peritoneal endoglin concentration ranged between 14.43- 15.65 ng/mL (median 15.04 ng/mL) which is higher than control group 7.42-10.26 ng/mL (median 8.84 ng/mL). A peritoneal endoglin concentration equal to or higher than 11 ng/mL could be used to predict endometriosis. Conclusion: Endoglin concentrations increased proportionally with the severity of endometriosis, and many be used as predictive factor of endometriosis cases.

Expression of endoglin and podoplanin in early and advanced oral squamous cell carcinoma

OBJECTIVES: Angiogenesis and lymphangiogenesis are correlated with tumor growth and lymph node metastasis in cases of oral squamous cell carcinoma (OSCC). Endoglin is one of the representative vascular endothelial cell markers. Podoplanin is also a representative marker used in order to detect lymphatic endothelial cells. The aim of this study was to determine the correlation between the expression of endoglin/podoplanin and clinical variables associated with OSCC progression. MATERIALS AND METHODS: Paraffin embedded tissue specimens from 21 patients diagnosed with OSCC were used in this study. Ten patients were diagnosed with early clinical stage (I or II) and 11 patients with advanced clinical stage (III or IV) OSCC. Five patients had positive lymph node involvement. Primary antibodies for endoglin and podoplanin were used to perform the immunohistochemical detection of the vascular and lymphatic endothelial cells. The expression of endoglin and podoplanin was examined by an image analysis program in the three most highly expressed regions of each specimen. RESULTS: The average endoglin expression was observed to be 1.691+/-0.920 in the advanced stage (III, IV) specimens and 0.797+/-0.583 in the early stage (I, II) specimens (P=0.020). The average expression of podoplanin was 0.286+/-0.228 in the advance stage (III, IV) specimens and 0.374+/-0.157 in the early stage (I, II) specimens (P>0.05). There was no statistically significant difference in the expression of endoglin and podoplanin, regardless of whether or not the lymph node was positive. CONCLUSION: The expression of endoglin was significantly higher in the advanced stage specimens than that in the early stage specimens. Therefore, we concluded that endoglin is a useful molecular marker for use in the evaluation of the progression of OSCC.

Levels of soluble endoglin in peripheral blood and intervillous space blood of patients with preeclampsia / 上海交通大学学报（医学版）

Objective To study the levels of soluble endoglin (sEng) in peripheral blood and intervillous space blood of patients with preeclampsia, and analyse the correlation between levels of sEng and clinical performance. Methods Levels of sEng in peripheral blood and intervillous space blood of 22 patients with preeclampsia (preeclampsia group, 12 cases of severe preeclampsia and 10 cases of mild preeclampsia) were detected by ELISA, and the correlation between levels of sEng and blood pressure, 24 h urine protein and fetal birth weight was analysed. Twenty-two normal pregnant women were served as control group. Results The sEng levels in peripheral blood and intervillous space blood of preeclampsia group were significantly higher than those of control group [ (31.89 ± 8.80) ng/mL vs (5.24 ± 1.60) ng/mL, P < 0.01; ( 37.74 ± 7.12) ng/mL vs (6.63 ±1.76) ng/mL, P < 0.01]. In preeclampsia group, the sEng levels in peripheral blood and intervillous space blood of severe preeclampsia were significantly higher than those of mild preeclampsia (P <0.01). In preeclampsia group, the sEng level in peripheral blood was significantly correlated with that in intervillous space blood of preeclampsia group (r = 0.876, P < 0.01) , neither was significantly correlated with blood pressure (P > 0.05), both were significantly correlated with 24 h urine protein (r = 0.729, P < 0.01; r = 0.743, P < 0.01) , and both were significantly correlated with fetal birth weight (r = - 0.736, P < 0.01; r = - 0.707, P < 0.01). Conclusion Levels of sEng in peripheral blood and intervillous space blood of patients with preeclampsia are significantly higher than those of normal pregnant women, and the levels of sEng are significantly correlated with the clinical performance of preeclampsia.

Lack of association of Endoglin insertion polymorphism in intracranial aneurysm in South Indian population.

Background : Endoglin , is a component of transforming growth factor-β complex. It is involved in vascular development and structural maintenance of the vessel wall. Conflicting reports on the association of a six base insertion polymorphism in intron 7 of the endoglin gene in intracranial aneurysms (IA) have been reported earlier. materials and Methods: A case-control study was designed to compare 102 South Indian patients with intracranial saccular aneurysms and 118 ethnically and geographically matched healthy controls. The frequency of the six base insertion polymorphism was assessed by heteroduplex analysis followed by direct sequencing. Results:Insertion allele count was 39 (19.1%) of 204 alleles in the patient group and 42 (17.8%) of 236 alleles in the control group. The INS allele frequency was similar to the frequency in Caucasian population, but it was significantly lower than the Japanese population ( P =0.01). There was also no relationship of this polymorphism in patients with single aneurysm (33/176 alleles) or those with multiple aneurysms (6/28 alleles). Conclusion:Six base insertion polymorphism in Endoglin gene was not found to be a risk factor for intracranial saccular aneurysms in the South Indian population. Ethnic-related differences were observed. This is the first report on any genetic mutation in intracranial aneurysms in Indian population.

Endoglin in assessing angiogenesis of epithelial ovarian tumor:report of 70 cases / 第三军医大学学报

Objective To investigate the significance of endoglin in the angiogenesis of ovarian carcinoma.Methods Immunohistochemical assay was used to investigate 70 tissue samples of pathologically identified epithelial ovarian tumor(including 31 specimen of benign and 39 of malignant)from December 2000 to December 2003 in our department using monoclonal antibodies against CD34 and endoglin.Microvessels density(MVD)was counted by experienced pathologists.Results No significant difference of MVD for CD34 was observed in the ovarian cystadenoma and ovarian carcinoma.In contrast,an increment of MVD for endoglin from low-grade to high-grade dysplasia and that from earlier stage to later stage was statistically significant.Conclusion Endoglin may be a valuable marker for assessing neovascularization in the process of ovarian carcinoma development and for predicting the risk of ovarian carcinoma development.