Endothelial Cell-specific Molecule-1 Research Articles

Pan-cancer analysis identifies ESM1 as a novel oncogene for esophageal cancer.

Recent studies highlight the crucial role of endothelial cell-specific molecule 1 (ESM1) in the development of multiple cancer types. However, its aberrant expression and prognostic value in human pan-cancer have largely not been described. In this study, we used The Cancer Genome Atlas (TCGA) analysis databases to explore the expression level and prognostic significance of ESM1 in 33 types of human cancer. ESM1 was shown to be over-expressed in 12 cancer types, including BLCA, BRCA, COAD, CHOL, ESCA, HNSC, KIRC, KICH, LIHC, STAD, THCA, and UCEC. The expression of ESM1 was significantly correlated with the overall survival (OS) of patients in CESC, ESCA, KIRC, and KIRP. In addition, high ESM1 level indicated poor disease-free survival (DFS) of patients with ACC, ESCA, PRAD, LIHC, KIRP, and UCS. Through comparative analysis, we discovered that ESM1 was dramatically up-regulated in esophageal cancer (ESCA) and associated with worse patient OS and DFS. The elevation of ESM1 in ESCA was confirmed by the datasets from Cancer RNA-Seq Nexus (CRN) and Gene Expression Omnibus (GEO). Based on Gene Set Enrichment Analysis (GSEA), we analyzed the co-expressed genes of ESM1 in ESCA, and found that ESM1 was closely implicated in cell proliferation and migration and the regulation of Janus kinase (JAK) signaling pathway. Functionally, knockdown of ESM1 significantly suppressed cell proliferation and migration, and decreased the protein level of JAK1. Taken together, our results suggest for the first time that ESM1 functions as an oncogene and may be a clinical biomarker and/or therapeutic target in ESCA.

Serum biomarkers of endothelial glycocalyx injury in canine parvoviral infection

Canine parvoviral enteritis (PVE) is one of the most common diseases in young dogs. A range of diseases and inflammatory conditions can cause endothelial glycocalyx (eGCX) disruption, therefore, this study aimed to determine the presence of eGCX damage in dogs with PVE using serum biomarkers of eGCX, and to evaluate their prognostic importance among survivor and non-survivor dogs. Twenty dogs diagnosed with PVE and 10 healthy dogs of both sexes, mixed-breed, and under 6 months of age were included in the study. Clinical examination, blood gas analysis, and complete blood cell counts of the dogs were performed. To detect the eGCX injury, serum endothelial cell-specific molecule-1 (ESM-1), syndecan-1 (SDC-1), angiopoietin-2 (Ang-2), and heparan sulfate (HS) levels were measured. Results showed that at the time of admission serum levels of ESM-1 were higher in dogs with PVE compared to that of the healthy dogs. Dogs with PVE were further assigned into two groups: survivors (n:10) and non-survivors (n:10). The ESM-1 had high sensitivity and specificity to differentiate between survivor and non-survivor dogs with values of 100% and 67%, respectively, with at an optimum cut-off point of ≥460 pg/mL. We concluded that higher levels of ESM-1 in dogs with PVE may indicate eGCX injury when compared to healthy dogs. Also, the high levels of serum ESM-1 in non-survivor dogs suggest that serum ESM-1 may carry some prognostic usefulness for predicting mortality in dogs with PVE.

The Role of Endocan in Selected Kidney Diseases.

Endocan, previously referred to as an endothelial-cell-specific molecule-1 (ESM-1) is a member of a proteoglycan family that is secreted by vascular endothelial cells of different organs, mainly lungs and kidneys. It is assumed to participate in endothelial activation and the triggering of inflammatory reactions, especially in microvasculatures. Thanks to its solubility in human fluids, i.e., urine and blood plasma, its stability and its low concentrations in physiological conditions, endocan has been proposed as an easily available, non-invasive biomarker for identifying and predicting the course of many diseases. Recently, endocan has been studied in relation to kidney diseases. In general, endocan levels have been linked to worse clinical outcomes of renal dysfunction; however, results are conflicting and require further evaluation. In this review, authors summarize available knowledge regarding the role of endocan in pathogenesis and progression of selected kidney diseases.

Endothelial Cell-Specific Molecule 1 Promotes Endothelial to Mesenchymal Transition in Renal Fibrosis.

The endothelial-to-mesenchymal transition (EndoMT) is involved in the complex pathogenesis of renal fibrosis. The soluble proteoglycan endothelial cell-specific molecule 1 (ESM1) is significantly upregulated in many tumor cells and cirrhosis-related disease. The role of ESM1 in renal fibrosis is unknown. This study investigates the role of ESM1 in renal fibrosis, using an in vivo unilateral ureteral obstruction (UUO) mouse model of renal fibrosis and in vitro mouse kidney MES 13 cells overexpressing ESM1. We observed that ESM1 overexpression significantly increased the motility and migration of MES 13 cells, independent of cell viability. In ESM1-overexpressing MES 13 cells, we also observed elevated expression of mesenchymal markers (N-cadherin, vimentin, matrix metallopeptidase 9 (MMP9)) and the fibrosis marker α-smooth muscle actin (α-SMA) and decreased expression of the endothelial marker vascular endothelial cadherin (VE-cadherin) and CD31. In a mouse model of fibrosis induced by unilateral ureter obstruction, we observed time-dependent increases in ESM1, α-SMA, and vimentin expression and renal interstitial collagen fibers in kidney tissue samples. These results suggest that ESM1 may serve as an EndoMT marker of renal fibrosis progression.

The Relationship Between the Level of Serum ESM-1 and Lp-PLA2 in Patients With Acute ST-Segment Elevation Myocardial Infarction.

Acute ST‐segment elevation myocardial infarction (STEMI) is the most lethal coronary heart disease with vascular endothelium dysfunction and inflammation in the disease development process. Endothelial cell‐specific molecule 1 (ESM‐1) and lipoprotein‐associated phospholipase A2 (Lp‐PLA2) are important for the diagnosis and characterization of STEMI. To date, no studies have reported the correlation between ESM‐1 and Lp‐PLA2 levels in patients with STEMI, which may be an important predictor of the fatal disease. To measure the level of serum ESM‐1 and Lp‐PLA2, and to evaluate the relationship and the clinical significance of these two biomarkers in patients with acute STEMI, 37 inpatients with acute STEMI were sequentially enrolled in the research group and 24 study objects with normal coronary artery function were included in the control group. The measurement of the relative parameters was done by enzyme‐linked immunosorbent assay using blood samples taken from the median cubital vein while the inpatients were enrolled. The levels of serum SEM‐1 and Lp‐PLA2 were significantly higher in patients with acute STEMI than in study objects with normal coronary artery function (P < 0.05). A significant correlation of serum SEM‐1 and Lp‐PLA2 was observed, leading to close linearity (r 2 = 0.8131, P < 0.0001). In conclusion, the endothelium dysfunction factor ESM‐1 and inflammatory factor Lp‐PLA2 are significantly higher and correlated in patients with acute STEMI. These two factors could be novel and effective biomarkers for acute STEMI diagnosis and evaluation.

Amniotic fluid concentrations of soluble endoglin and endothelial cell-specific molecule-1 in pregnancies complicated with neural tube defects.

Objective To determine the concentrations of soluble endoglin (sCD105) and endothelial cell-specific molecule-1 (ESM-1) in the amniotic fluid (AF) of pregnant women, and to investigate the relationship between these concentrations and neural tube defects (NTDs). Methods AF concentrations of sCD105 and ESM-1 were measured in the study group, which included 60 pregnant women complicated with NTDs, and 64 pregnant women with unaffected healthy fetuses (control group). The AF concentrations of sCD105 and ESM-1 in both groups were measured using enzyme-linked immunosorbent assay and compared. Results There were no significant differences in terms of the mean AF concentrations of sCD105 and ESM-1 between the groups (P=0.141, P=0.084, respectively). There was a significant difference between the AF sCD105 concentrations in those with gestational age <24 weeks (n=101) and ≥24 weeks (n=23) (X̅<24=76.35±126.62 vs. X≥24=39.87±58.32, P=0.041). AF ESM-1 concentrations were found to be statistically significant in the gestational age <22 weeks (n=90) and ≥22 weeks (n=34) groups (X̅<22=135.91±19.26 vs. X̅≥22=148.56±46.85, P=0.035). A positive and low-level relation at a statistically significant level was determined between the gestational age and AF ESM-1 concentration in the study group (r=0.257; P=0.048). Conclusion AF concentrations of sCD105 and ESM-1 were not associated with the development of NTDs. Unlike studies that reported that ESM-1 concentrations decreased in maternal plasma with increased gestational age, we determined an increase that was proportionate to gestational age in AF.

Endocan expression correlated with total volume of coronary artery dilation in patients with coronary artery ectasia.

IntroductionInflammation and angiogenesis disturbances are considered as factors contributing to the development of coronary artery ectasias (CAE). Endocan (endothelial cell-specific molecule-1 – ESM-1) regulates both inflammatory and angiogenetic processes. However, there are no data about the correlation between endocan level and the severity of CAE measured with total volume of coronary artery dilation.AimTo assess whether the severity of the inflammatory process measured as endocan concentration correlates with the total volume of CAE.Material and methodsWe selected prospectively a total of 43 consecutive patients with coronary artery ectasia from 2240 patients who underwent coronary angiography in our center. Determination of endocan was performed by using the Human Endothelial cell-specific Molecule 1 (ECSM1/ENDOCAN) ELISA Kit. 3D QCA (three-dimensional quantitative coronary angiography) was used for coronary lesion and aneurysm quantification. The total volume of dilation was defined as the volume of all aneurysms and ectasias of coronary arteries in 1 patient.ResultsThe mean volume of all aneurysms in 1 patient was 677 ±878.7 mm3. The total aneurysm volume was positively strongly correlated with endocan concentration (Pearson correlation coefficient: 0.811; 2-tailed p < 0.001).ConclusionsEndocan is a potential marker of vascular wall damage mainly as a result of inflammation in the course of atherosclerosis, but also vascular remodeling as a result of a disturbance of pro- and anti-angiogenic processes. Endocan level reflects the intensity of the above processes and therefore correlates with the severity of CAE, measured as the total volume of dilation.

Impact of the ESM-1 Gene Expression on Outcomes in Stage II/III Gastric Cancer Patients Who Received Adjuvant S-1 Chemotherapy.

Endothelial cell-specific molecule-1 (ESM-1) is a soluble proteoglycan which has important role in various biological events. We investigated the impact of the ESM-1 expression in cancer tissues on outcomes in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy. The ESM-1 mRNA expression in cancerous tissues and adjacent normal mucosa from 253 patients was measured. The associations between the ESM-1 gene expression and the survival and clinicopathological features were investigated. A significant association was observed between high ESM-1 expression and undifferentiated adenocarcinoma. The overall survival curve was significantly lower in patients with high ESM-1 expression than in those with low expression (p=0.005). High ESM-1 expression was a significant independent prognosticator (HR=2.291, p=0.007). ESM-1 gene expression in cancerous tissues is an important prognosticator in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy.

Determination the Role of Endothelial Cell-Specific Molecule-1(ESM-1) in Childhood Bronchial Asthma

Background Endothelial Cell-Specific Molecule-1 (ESM-1) is a 50 kDa soluble proteoglycan that is produced mainly the vascular endothelial cells of the kidney and lung. It is produced by the effects of proangiogenic and pro-inflammatory cytokines, and it indicates activation and dysfunction of the vascular endothelium. We aimed to detect the role of ESM-1 in children with asthma. Materials and Methods This study is a prospective cross sectional study and include 50 child (32 with mild persistent, 18 with moderate persistent asthma (patients) and 30 healthy children served as controls, both groups were selected from outpatient pulmonology clinic and inpatient pediatric department at children hospital, Minia University, Egypt, from 2016 to 2018; and were subjected to: detailed clinical examination, lung function test, complete blood picture and measurement of level of ESM-1 in serum. Results Level of ESM-1 was increased in asthmatic children compared to the controls (p=0.001). Also, the level of ESM-1 in children suffering from moderate persistent asthma was markedly higher than those with mild persistent asthma (p=0.001). In addition, ESM-1 level was positively correlated with eosinophil counts (r=0.79, p=0.01), but had negative correlation with lung functions FEV1 and PEFR (r=- 0.89, - 0.84, p=0.001). Conclusion ESM-1 level was increased in asthmatic children suggesting that it may have a role in asthma, furthermore, it was associated with decreased lung function indicating that it is considered as an indicator of severe asthma.

Exosomal MicroRNA-9-3p Secreted from BMSCs Downregulates ESM1 to Suppress the Development of Bladder Cancer

Exosomes, carriers to transfer endogenous molecules, derived from bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to play a role in the progression of bladder cancer. Here we aimed to test the functional mechanism of microRNA-9-3p (miR-9-3p)-containing exosomes derived from BMSCs in bladder cancer. BMSCs were cocultured with bladder cancer cells, and exosomes secreted from BMSCs were identified. Next, the expression of miR-9-3p and endothelial cell-specific molecule 1 (ESM1) in bladder cancer tissues and cells was determined. Then effects of miR-9-3p and ESM1 via BMSC-derived exosomes on bladder cancer cell viability, migration, invasion, and apoptosis were determined by loss- and gain-of-function experiments and on in vivo tumor growth, and metastasis was assessed in nude mice. miR-9-3p expression was decreased and ESM1 was increased in bladder cancer. BMSCs inhibited bladder cancer cell viability, migration, and invasion, and induced apoptosis, whereas the addition of exosome secretion inhibitor GW4869 achieved the opposite effects. Moreover, exosomal miR-9-3p upregulation or ESM1 silencing suppressed bladder cancer cell viability, migration, and invasion; induced cell apoptosis; and inhibited in vivo tumor growth and metastasis. Taken together, BMSC-derived exosomal miR-9-3p suppressed the progression of bladder cancer through ESM1 downregulation, offering a potential novel therapeutic target for bladder cancer therapy.

Endothelial cell-specific molecule-1 as an invasiveness marker for pituitary null cell adenoma

BackgroundEndothelial cell-specific molecule-1 (ESM-1) is a biomarker associated with tumor progression in pituitary adenoma. We specifically focused on one type of pituitary adenoma, namely null cell adenoma (NCA) and evaluated the relationship between invasion and ESM-1 expression in both vascular endothelial and adenoma tissues.MethodsTissue samples from 94 patients with pituitary NCA were obtained through microscopic transsphenoidal resection. Tumor size and invasion were determined through preoperative magnetic resonance imaging. Immunohistochemical staining was performed to detect ESM-1 expression. ESM-1 index of ≥3 was defined as high expression.ResultsSigns of invasion were observed in 46 (47.9%) of the 94 patients. Significant differences were observed in the invasion state and maximum tumor diameter between high and low expression of ESM-1 in vascular endothelial tissues (both P < 0.05). Significant positive associations were noted between ESM-1 expression in vascular endothelial tissues and tumor invasion (P = 0.002) and tumor size (P = 0.020). However, only tumor size was associated with ESM-1 expression in adenoma tissues (P = 0.016).ConclusionIn NCA, a significant positive association between tumor invasion and ESM-1 expression was observed only in vascular endothelial tissues, suggesting that tumor progression occurs mainly through ESM-1-associated mechanism.

Identification of ESM1 overexpressed in head and neck squamous cell carcinoma

BackgroundEndocan, also known as endothelial cell specific molecule-1 (ESM1), is a 50 kDa soluble proteoglycan which is frequently overexpressed in many cancer types. Whether it is dysregulated in head and neck squamous cell carcinoma (HNSCC) has not been investigated.MethodsWe analyzed the expression of ESM1 using bioinformatics analysis based on data from The Cancer Genome Atlas (TCGA), and then validated that ESM1 was significantly overexpressed in human HNSCC at the protein level using immunohistochemistry. We also analyzed the genes co-expressed with ESM1 in HNSCC.ResultsThe most correlated gene was angiopoietin-2 (ANGPT2), a molecule which regulates physiological and pathological angiogenesis. Several transcription factor binding motifs including SMAD3, SMAD4, SOX3, SOX4, HIF2A and AP-1 components were significantly enriched in the promoter regions of the genes co-expressed with ESM1. Further analysis based on ChIP-seq data from the ENCODE (Encyclopedia of DNA Elements) project revealed that AP-1 is an important regulator of ESM1 expression.ConclusionsOur results revealed a dysregulation of ESM1 and a potential regulatory mechanism for the co-expression network in HNSCC.

Risk stratification and prognostic evaluation of endothelial cell-specific molecule1, von Willebrand factor, and a disintegrin-like and metalloprotease with thrombospondin type 1 motif for sepsis in the emergency department: An observational study.

This study evaluated endothelial cell-specific molecule1 (endocan), von Willebrand factor (vWF), and A disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS-13), alone or in combination, in the risk stratification and prognosis prediction of patients with sepsis. Clinical data of 301 patients were prospectively analyzed, and divided into systemic inflammatory reaction syndrome, sepsis, severe sepsis, and septic shock groups. A total of 40 healthy individuals were studied as the control group. Endocan, vWF, ADAMTS-13, vWF/ADAMTS-13, and procalcitonin levels were measured, and Acute Physiology and Chronic Health Evaluation (APACHE II) score, Mortality in Emergency Department Sepsis (MEDS) score as well as Sequential Organ Failure Assessment (SOFA) score were calculated. The all-cause death or survival of each patient was recorded during the 28-day follow-up. The endocan, vWF, and vWF/ADAMTS-13 levels significantly increased in patients and were positively correlated with disease severity. On the first day of admission, MEDS score, ADAMTS-13, and vWF/AMAMTS-13 ratio were independent predictors for 28-day mortality from sepsis. Moreover, the combination of vWF/ADAMTS-13 ratio with MEDS score improved the accuracy in predicting the 28-day mortality from sepsis. On day 5, endocan, vWF, ADAMTS-13, and vWF/ADAMTS-13 ratio were independent predictors for the 28-day mortality from sepsis, while the combined use of endocan and vWF/ADAMTS-13 ratio improved the prognostic value of individual indicators. Endocan, vWF, ADAMTS-13, and vWF/ADAMTS-13 ratio are valuable in the risk stratification and prognostic evaluation of sepsis as novel biomarkers.

Comparison of sepsis severity markers in emergency department

Objective This study was to evaluate the values of endothelial cell-specific molecule1 (endocan),von Willebrand factor (vWF),andA disintegrin-like and metalloprotease with thrombospondin type 1 motif(ADAMTS-13), alone or in combination, in the risk stratification and disease severity assessment of patients with sepsis via comparing the differences of these markers in patients with systemic inflammatory reaction syndrome (SIRS), sepsis, severe sepsis, or septic shock, and healthy volunteers. Methods Clinical data of 301 patients with SIRS or sepsis treated in our Emergency Department from October 2014 to October 2015, were prospectively analyzed. These patients were divided into SIRS, sepsis, severe sepsis, and septic shock groups. 40 healthy individuals were selected as control. Endocan, vWF, ADAMTS-13, vWF/ADAMTS-13, and Procalcitonin (PCT) levels were measured, and APACHEⅡ score, MEDS score as well as SOFA score were calculated. The all-cause death or survival of each patient was recorded during the 28-day follow-up. Results The endocan, vWF, and vWF/ADAMTS-13 levels significantly increased in patients with SIRS, sepsis, severe sepsis, or septic shock and were positively correlated with disease severity, and were also positively correlated with MEDS score, APACHEⅡ score, SOFA score. On the other way, the ADAMTS-13 level gradually declined during disease progression and was negatively correlated with the disease severity, it was also negatively correlated with MEDS score, APACHEⅡ score, SOFA score. Conclusions Endocan, vWF, ADAMTS-13, and vWF/ADAMTS-13 ratio are valuable in the risk stratification and disease severity evaluation of sepsis, providing novel sepsis biomarkers in clinic. Key words: Endothelial cell specific molecule-1; von Willebrand factor; A disintegrin-like and metalloprotease with thrombospondin type 1 motif; Sepsis; Risk stratification

Placental Growth Factor and Endothelial Cell-Specific Molecule 1 Levels in Discordant and Concordant Twins and Their Effects on Fetal Growth

Objective: We explored whether fetal twin growth was related to the levels of placental growth factor (PGF) and endothelial cell-specific molecule 1 (ESM-1) and sought correlations between cord blood PGF and ESM1 levels and birth weight discordance. Methods: This was a prospective study. We evaluated 79 pairs of twins, thus 158 infants. Twenty-nine (37%) twins were naturally conceived; the remaining 50 (63%) resulted from assisted reproduction. Results: Nine (11%) sets of twins were monochorionic. Eighteen of the 79 twin sets (22%) were discordant. We found a positive correlation between PGF and ESM-1 levels (r = 0.51, p = 0.001) and between discordance and PGF level (r = 0.430, p = 0.001). Conclusion: The growth discordance may not be attributable to the different PGF levels, but the difference in PGF level may be a consequence.

Expression of endocan and vascular endothelial growth factor in recurrent minor aphthous ulcers.

BackgroundRecurrent aphthous ulcers (RAU) are common painful inflammatory lesions of the mucous lining of the mouth. Endocan, previously identified as endothelial cell specific molecule-1, is implicated as a vital player in the regulation of several inflammatory processes. A number of inflammatory cytokines and pro-angiogenic growth factors including VEGF upregulate endothelial cells synthesis and expression of endocan.Material and MethodsClinical scores of pain and ulcer size as well as level of endocan and VEGF were determined in swaps from aphthous ulcer and contra lateral normal mucosa in 30 patients (nine males and twenty one females) with age ranging from 18 to 45 years and mean age is 31.5 years.ResultsIn the early days of ulcer development, ulcer showed statistically significantly higher mean endocan (8.2 ±5.3) and VEGF levels (1220.7 ±294.6) than control healthy mucosal site (1.1 ±0.5) and (518.6 ± 61.7) respectively. An increase in endocan is associated with an increase in pain score and vice versa. A statistically significant positive correlation were also found between endocan and VEGF levels.ConclusionsEndocan and VEGF are strongly associated with the destructive phase of minor aphthous ulcers especially Endocan which was positively correlated with pain severity. Key words:Endocan, ESM-1, VEGF, Recurrent Apthous Ulcer.

A novel marker relationship between carotid intima media thickness and disease activity score-28 in patients with rheumatoid arthritis: Human endothelial cell-specific molecule-1.

Background/aim Human endothelial cell-specific molecule-1 (endocan) is a marker of vascular endothelial dysfunction that may be used in the evaluation of inflammatory-associated atherosclerotic lesions. Endocan may be a marker for the evaluation of atherosclerosis and disease activity in rheumatoid arthritis (RA) patients.Materials and methodsWe included 39 RA patients assessed according to the American College of Rheumatology/European League Against Rheumatology 2010 diagnostic criteria and recruited 30 age- and sex-matching healthy subjects for the control group.ResultsEndocan values were 14.11 ± 3.27 for the RA patients and 12.10 ± 2.92 for the controls. The endocan values of the patients were significantly higher than those of the control group (P = 0.009). In the correlation analysis, endocan showed a significantly positive correlation with disease activity score-28 (r = 0.386, P = 0.029) and carotid intima–media thickness (cIMT) (r = 0.419, P = 0.008). Linear regression analysis revealed that there was an independent relationship between endocan and cIMT (P = 0.029).Conclusion Endocan can be a marker for early atherosclerosis and disease activity in RA patients.

Immunohistochemical expression of endocan, as a marker of assessment of angiogenic potential in benign vascular lesions (hemangioma, lymphangioma and lobular capillary hemangioma) of head and neck region

BACKGROUND: Vascular tumors are a heterogeneous group of diseases with biological behavior ranging from a hamartomatous growth to frank malignant. The pathophysiology of lymphangioma, vascular malformation and hemangioma is interconnected, blood vessels known to be the site of origin of hamartomas, venous malformations and some neoplasms as benign, tumor-like growth of vessels (hemangiomas). Angiogenesis is the process of formation of new blood vessels from an existing structure.&#x0D; Aims of study Assessment of angiogenic potential in benign vascular lesions (hemangioma, lymphangioma and lobular capillary hemangioma) of head and neck region.&#x0D; Materials and Methods: Twenty-two formalin-fixed paraffin-embedded tissue blocks of Hemangioma/vascular malformation, thirty of lobular capillary hemangioma and another twenty of lymphangioma to be stained with Endothelial cell-Specific Molecule-1 (ESM-1) monoclonal antibody. &#x0D; Results: Microvessel density expressed by Endothelial cell-Specific Molecule-1 (ESM-1) immunomarker was found in all cases with mean density of (37.44±23.16) for lobular capillary hemangioma and (25.02±13.89) for hemangioma and (6.34±3.52) for lymphangioma. According to post hoc test ESM-1 marker expression showed a high significant difference between (hemangioma and lymphangioma=0.001), (lymphangioma, pyogenic granuloma=0.000), and it was significantly different between (hemangioma, pyogenic granuloma=0.011)&#x0D; Conclusions: The obvious capillary growth in lobular capillary hemangioma revealed that lobular capillary hemangioma showed the highest activity of angiogenic potential in comparison to hemangioma and lymphangioma.

Serum Level of Endothelial Cell-Specific Molecule -1 (ESM -1) as a New Potential Biomarker for Rheumatoid Arthritis Disease Activity

Background:Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by destruction of the joint cartilage and bone. Endothelial dysfunction (ED) in RA may be related to disease activity. Our objective is to explore serum levels of endothelial cell-specific molecule-1 (ESM-1) as a biomarker for RA disease activity.Methods:A cross-sectional study was carried out and included 83 adult patients with RA, in addition to 20 healthy subjects (age and sex-matched) as a control group. Based on Disease Activity Score in 28 joints (DAS-28), the patient's group was subdivided into four subgroups(remission, mild, moderate and severe disease activity state). The demographic &amp; clinical data, BMI, DAS-28 and Serological assessment [Erythrocyte Sedimentation Rate (ESR), CRP, Rheumatoid Factor (RF) and Anti-Citrullinated Peptide Antibody (ACPA)] were recorded. ESM-1was assayed for all participants.Results:Serum levels of ESM1 were significantly higher in the patient group than the control group (P&lt; 0.0001). ESM-1 serum levels were significantly higher in patients with severe disease activity subgroup compared with patients with remission and mild disease activity subgroups (P&lt; 0.0001). ESM-1 was positively and significantly correlated with DAS-28 score, The Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Larsen score (P= 0.002, 0.0001 &amp; 0.0001 respectively).Conclusion:ESM-1 could be a biomarker for RA disease activity.

Enhanced Function of Induced Pluripotent Stem Cell-Derived Endothelial Cells Through ESM1 Signaling.

The mortality rate for (cardio)‐vascular disease is one of the highest in the world, so a healthy functional endothelium is of outmost importance against vascular disease. In this study, human induced pluripotent stem (iPS) cells were reprogrammed from 1 ml blood of healthy donors and subsequently differentiated into endothelial cells (iPS‐ECs) with typical EC characteristics. This research combined iPS cell technologies and next‐generation sequencing to acquire an insight into the transcriptional regulation of iPS‐ECs. We identified endothelial cell‐specific molecule 1 (ESM1) as one of the highest expressed genes during EC differentiation, playing a key role in EC enrichment and function by regulating connexin 40 (CX40) and eNOS. Importantly, ESM1 enhanced the iPS‐ECs potential to improve angiogenesis and neovascularisation in in vivo models of angiogenesis and hind limb ischemia. These findings demonstrated for the first time that enriched functional ECs are derived through cell reprogramming and ESM1 signaling, opening the horizon for drug screening and cell‐based therapies for vascular diseases. Therefore, this study showcases a new approach for enriching and enhancing the function of induced pluripotent stem (iPS) cell‐derived ECs from a very small amount of blood through ESM1 signaling, which greatly enhances their functionality and increases their therapeutic potential. Stem Cells 2019;37:226–239