Endocan Expression Research Articles

A low testosterone level impairs erectile function by increasing endocan expression in rat penile corpus cavernosum.

The mechanism by which a state of low testosterone leads to erectile dysfunction (ED) has not been determined. Endocan is a novel marker of endothelial function. However, whether endocan is involved in the regulation of erectile function under low testosterone levels remains unclear. In this study we sought to determine whether a low-testosterone state inhibits erectile function by regulating endocan expression in the endothelial cells of the rat penile corpus cavernosum. Thirty-six male Sprague-Dawley rats aged 8 weeks were randomly assigned to 6 groups (n = 6 per group) as follows: (1) control, (2) castration, (3) castration + testosterone treatment (treated with 3mg/kg testosterone propionate per 2days), (4) control + transfection (4weeks after castration, injected with lentiviral vector (1 × 108 transduction units/mL, 10μL), (5) castration + transfection, or (6) castration + empty transfection. One week after the injection, we measured the maximal intracavernous pressure/mean arterial pressure (ICPmax/MAP), serum testosterone and nitric oxide (NO) levels, and the expression of endocan, phospho-endothelial NO synthase (p-eNOS), eNOS, phospho-protein kinase B (p-AKT), and AKT in the rat penile corpus cavernosum. Under a low-androgen state, the expression of endocan in the rat penile corpus cavernosum was significantly increased, which inhibited the AKT/eNOS/NO signaling pathway and resulted in ED. In the castration group, the expression of endocan in the rat penile corpus cavernosum was significantly higher than that in the control group (P < .05). Additionally, the levels of p-AKT/AKT, p-eNOS/eNOS, and NO in the rat penile corpus cavernosum and ICPmax/MAP were significantly lower in the castration group than in the control group (P < .05). In the castration + transfection group compared with the castration group there was a significant decrease in the expression of endocan (P < .05) and an increase in the ratios of p-AKT/AKT, p-eNOS/eNOS, and ICPmax/MAP (P < .05) in the rat penile corpus cavernosum. Downregulating the expression of endocan in the penile corpus cavernosum may be a feasible approach for treating ED caused by hypoandrogenism. The results of this study indicte that endocan may affect NO levels and erectile function through multiple signaling pathways, but further experiments are needed to clarify the relationship between endocan and androgens. A low-testosterone state inhibits the AKT/eNOS/NO signaling pathway by increasing the expression of endocan in the rat penile corpus cavernosum and impairing erectile function in rats. Decreasing the expression of endocan in the penile corpus cavernosum can improve erectile function in rats with low testosterone levels.

Vascular endothelial growth factor and endocan expression in adrenal cortical tumors and their relationship with histopathological prognostic parameters.

The aim of this study was to determine the tissue expressions of vascular endothelial growth factor (VEGF) and endocan in adrenal cortical tumors and the factors associated with them. The study included 6 subjects with adrenocortical adenoma (ACA), 7 subjects with adrenocortical carcinoma (ACC), and 13 control subjects with a normal adrenal cortex. The status of VEGF and endocan expression was determined by the proportions of cells staining on a scale ranging from negative (not staining at all) to strongly positive. VEGF expression was detected in 1 (16.7%) of 6 subjects in the ACA group and in 6 (85.7%) of 7 subjects in the ACC group. VEGF expression was not detected in any of the subjects in the control group. Endocan expression was detected in 6 (100%) of 6 subjects in the ACA group and in 7 (100%) of 7 subjects in the ACC group, while it was detected in only 4 (30.7%) of 13 subjects in the control group. VEGF was expressed with a high frequency in subjects with ACC and with a low frequency in subjects with ACA, but it was not expressed in subjects with normal adrenal cortex tissue. Although endocan was expressed with a higher frequency in subjects with ACC and ACA, it was also expressed in subjects with normal adrenal cortex tissue. The percentage of cells expressed endocan in subjects with ACC was also significantly higher than in subjects with both ACA and normal adrenal cortex.

Investigation of maternal serum endocan concentrations in pregnant women with gestational diabetes mellitus; a prospective case-control study

Objective We aimed to investigate the maternal serum endocan concentrations in pregnant women diagnosed with Gestational Diabetes Mellitus (GDM) and to investigate the usability of serum endocan in GDM screening. Methods This prospective case-control study was conducted with 160 pregnant women. The GDM group consisted of 80 pregnant women who had 75 g OGTT between the 24th and 28th weeks of pregnancy and were diagnosed with GDM. The control group consisted of 80 healthy pregnant women who were matched with the GDM group in terms of age and body mass index (BMI) and had a normal 75 g OGTT result. Serum endocan concentrations were evaluated between 24 and 28 weeks of gestation in all participants and the groups were compared in terms of serum endocan concentrations. Results The median maternal serum endocan concentration was found to be significantly higher in the GDM group than in the control group (498 ng/L, and 467 ng/L, respectively, p = 0.024). In the subgroup analysis according to the BMI of the participants, the highest median maternal serum endocan concentration (513 ng/L) was found in the overweight GDM group. ROC analysis was performed to determine the value of maternal serum endocan concentration in predicting GDM. AUC analysis of maternal serum endocan for estimation of GDM was 0.603 (p = 0.024, 95% CI = 0.515 − 0.691). The optimal threshold value for maternal serum endocan concentration was determined as 376 ng/L with 88.75% sensitivity and 32.5% specificity. Conclusion Although serum endocan does not have high enough specificity to be used as an alternative to OGTT in GDM screening between 24 and 28 weeks of gestation, we think that it is somehow involved in the pathogenesis of GDM. The contribution of placental endocan expression to the serum concentration and the effect of blood glucose regulation on serum endocan concentration in GDM remain to be investigated.

Expression of endocan and vascular endothelial growth factor and their correlation with histopathological prognostic parameters in pheochromocytoma.

Endocan and vascular endothelial growth factor (VEGF) are markers expressed in various cancer types that are highly vascular, and they have prognostic significance for these cancers. In this study, we aimed to show the expression of endocan and VEGF in pheochromocytoma tumor tissues and to evaluate their correlations with histopathological parameters. Thirty-eight patients who had been operated for pheochromocytoma were included in the study. As the control group, 28 subjects whose specimens contained normal adrenal medulla tissue were included. The formalin-fixed paraffin-embedded specimens of pheochromocytoma patients were evaluated for Pheochromocytoma of the Adrenal gland Scaled Score (PASS). Sections were then stained for immunohistochemical analysis. The degree of endocan and VEGF positivity was determined by the proportion of stained cells on a negative to strong scale. Endocan (p < 0.001) and VEGF (p = 0.004) expressions were found to be significantly higher in the pheochromocytoma group than in the control group. In the pheochromocytoma group, total PASS score (r = 0.714; p < 0.001) and most of the PASS score components were positively correlated with the level of endocan expression. Median Ki-67 index (p = 0.010), total PASS score (p < 0.001), tumor cell spindling (p = 0.048), and nuclear pleomorphism (p = 0.030) were higher in pheochromocytoma with VEGF expression than in those without. If our findings are supported by studies with a larger sample size, we think that endocan has the potential to be used both as a tumor marker and in predicting malignancy potential in patients with pheochromocytoma, and that the detection of VEGF expression in these tumors is also associated with an increase in malignancy potential.

Placental Endocan Expression in Woman With Preeclampsia and its Relation With Maternal and Fetal Outcomes: A Cross-section Study

Objectives: This study aimed to determine placental endocan expression in women with preeclampsia (PE) and its relation to fetal and maternal outcomes. Materials and Methods: This cross-sectional study was carried out at the Obstetrics Department/Al-Yarmouk Teaching Hospital from January 2020 to October 2020. The study included 90 pregnant inpatient women with PE. The participants were divided into 3 groups including 30 patients with severe PE, 30 non-severe PE, and 30 normotensives. After delivery, placental endocan expression was determined immunohistochemically. Results: The study showed that endocan was expressed in 44 patients’ placenta, all of them were hypertensive vs. 46 negatives for endocan (P=0.001), this expression correlated with adverse maternal outcomes including HELLP (haemolysis, elevated liver enzymes, and low platelets count) syndrome (9.1%), Placental abruption (13.6%) and increase rate of CS (63.6%), as well as adverse fetal outcomes (P=0.001). included stillbirth (13.6%), birth weight &lt;2500 g (68.2%), Apgar score in 1 min &lt;7 (63.6%) and in 5 minutes &lt;7 (31.8), admission to neonatal intensive care unit (NICU) (31.8%), and (68.2%) delivered preterm. Conclusions: This study showed a higher expression of endocan in the placenta of women with PE, and it had a positive correlation with adverse maternal and fetal outcomes.

Endocan Knockdown Down-Regulates the Expression of Angiogenesis-Associated Genes in Il-1ß Activated Chondrocytes.

Endocan is a small soluble proteoglycan (PG) known to be involved in inflammation and angiogenesis. Increased endocan expression was found in the synovia of arthritic patients and chondrocytes stimulated with IL-1ß. Considering these findings, we aimed to investigate the effects of endocan knockdown on the modulation of pro-angiogenic molecules expression in a model of IL-1ß-induced inflammation in human articular chondrocytes. Endocan, VEGF-A, MMP-9, MMP-13, and VEGFR-2 expression was measured in both normal and endocan knockdown chondrocytes stimulated with IL-1ß. VEGFR-2 and NF-kB activation were also measured. Results have shown that endocan, VEGF-A, VEGFR-2, MMP-9, and MMP-13 were significantly up-regulated during IL-1ß-induced inflammation; interestingly, the expression of such pro-angiogenic molecules and NF-kB activation were significantly reduced by endocan knockdown. These data support the hypothesis that endocan released by activated chondrocytes may be involved in the mechanisms that stimulate cell migration and invasion, as well as angiogenesis, in the pannus of arthritic joints.

Endocan Promotes Pro-Tumorigenic Signaling in Lung Cancer Cells: Modulation of Cell Proliferation, Migration and lncRNAs H19 and HULC Expression.

Endocan is a circulating proteoglycan secreted by several cell lines and identified as a potential biomarker of inflammation and angiogenesis. Endocan-increased expression has been found in a broad spectrum of human tumors, including lung cancer, and is associated with a poor prognosis. To elucidate the possible mechanism, this study aimed to investigate the role of endocan in non-small-cell lung carcinoma (NSCLC) using an in vitro model of cultured cells. Endocan expression was knocked down by using a specific small interfering RNA. The effects of endocan knockdown have been evaluated on VEGF-A, VEGFR-2, HIF-1α, the long non-coding RNAs H19 and HULC expression, and AKT and ERK 1/2 degree of activation. Cell migration and proliferation have been studied as well. VEGF-A, VEGFR-2, HIF-1α, and the long non-coding RNAs H19 and HULC expression were significantly affected by endocan knockdown. These effects correlated with a reduction of cell migration and proliferation and of AKT and ERK 1/2 activation. Our findings suggest that endocan promotes a more aggressive cancer cell phenotype in NSCLC.

Elevated expression of endocan in the development of cervical squamous neoplasia of the uterus.

Accumulated evidence has shown that endocan, which was originally called endothelial cell-specific molecule-1, is an attractive prognostic factor in a variety of cancers. However, the relevance of endocan expression in human malignancies remains to be clarified. In the present study, the expression of endocan in cervical squamous neoplasia of the uterus, including low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), as well as in invasive squamous cell carcinoma was examined by immunohistochemistry. Endocan was not sufficiently expressed in the normal cervical epithelium. Endocan expression was present in LSIL cases but was limited to basal and parabasal areas of the cells. HSIL cases exhibited strong expression of endocan with widely distributed expression toward the epithelial surface. In contrast, further strong expression of endocan was not observed in patients with invasive carcinoma. This study is the first study showing increased expression of endocan in precancerous dysplastic lesions and malignancy of the cervix. The data suggest that a high expression level of endocan potentially contributes to the development of cervical squamous neoplasia of the uterus.

Can endocan serve as a molecular “hepatostat” in liver regeneration?

BackgroundIntriguingly, liver regeneration after injury does not induce uncontrolled growth and the underlying mechanisms of such a “hepatostat” are still not clear. Endocan, a proteoglycan, was implicated in liver regeneration. It can support the function of hepatocyte growth factor/scatter factor in tissue repair after injury. Endostatin, a 20 kDa C-terminal fragment of collagen XVIII, may modulate the cessation of liver regeneration. eEF2K, a protein kinase that regulates protein synthesis, can regulate angiogenesis. Thus, we investigated the role of endocan, endostatin and eEF2K during normal liver regeneration.MethodsSerum samples and regenerating remnant liver tissues were obtained on various days after partial hepatectomy in rats. mRNA expression levels of Vegf and Pcna were analyzed in addition to immunohistochemical evaluations. Liver tissue protein levels of endostatin, endocan and p-eEF2K/eEF2K were determined with Western blot. Serum levels of endostatin and endocan were assessed with ELISA.ResultsPcna expression level in residual liver tissues peaked on day-1, while Vegf expression reached its highest level on days 1–3 after partial hepatectomy (70%). Endocan activity declined gradually on days 1–7. The decrease in liver endocan expression was accompanied by an increase in serum endocan levels. Partial hepatectomy induced a rapid increase in liver endostatin levels. Following its surge on day-1, endostatin expression gradually declined, which was accompanied by a peak in serum endostatin. Finally, partial hepatectomy was shown to regulate eEF2K; thus, increasing protein translation.ConclusionsWe revealed possible mechanistic insights into liver regeneration by examining the associations of Pcna, Vegf, endocan, endostatin, eEF2K with hepatic regeneration after partial hepatectomy. Indeed, endocan might serve as a useful biomarker to monitor clinical prognosis in a plethora of conditions such as recovery of donor’s remaining liver after living-donor liver transplant. Whether endocan might represent a strategy to optimize liver regeneration when given therapeutically needs to be investigated in future studies.

Expression of the angiogenesis markers endocan in Cushing's syndrome due to cortisol producing adenoma.

In this study, we aimed to investigate the endocan expression in tissue samples of patients diagnosed with Cushing's syndrome (CS) due to Cortisol-Producing-Adenoma (CPA) and compare it with normal adrenal cortex tissue, and also to evaluate the correlations of endocan expression with clinical and histopathological features. 11 patients who were operated for CS due to CPA between 2009-2021 and 14 control subjects with normal adrenal cortex were included in the study. Demographic, laboratory and clinicopathological data of the patients were recorded. Sections of 4-5 µm thickness were taken from paraffin blocks of patients diagnosed with CS due to CPA and control subjects with normal adrenal cortex tissue. The sections were then stained in a closed system automatic immunohistochemical staining device to perform immunohistochemical analysis. The endocan positive grade were determined based on the proportion of stained cells on a scale of negative to strong. The number of subjects with positive endocan expression and the mean endocan expression level in the CS group were significantly higher than the control group (p = 0.005, p < 0.001, respectively). No correlation was found between endocan expression and clinical and histopathological features. According to the results of our study, endocan overexpression in CPA tissues may be related to the hormonal functionality of CPA.

Increased endocan expression as a biomarker of endothelial dysfunction in patients with metabolic syndrome.

Increased endocan expression as a biomarker of endothelial dysfunction in patients with metabolic syndrome.

Empagliflozin induces endocan expression and alleviates NAFLD through regulation of NF-κB pathway

Empagliflozin induces endocan expression and alleviates NAFLD through regulation of NF-κB pathway

Significance of Endocan Expression in Various Types of Epithelial Ovarian Tumors.

Background & Objective:Ovarian cancer is associated with the highest mortality rate among gynecologic malignancies. Despite new therapeutic strategies, ovarian cancer still has a high risk of metastasis and mortality. Endocan is a newly identified endothelial cell activation marker, which is responsible for angiogenesis, tumor invasion, and aggressive behavior of tumors. The aim of this study was to assess Endocan expression in different types of ovarian tumors and to identify its relationship with clinicopathologic characteristics of ovarian tumors. Methods:This cross-sectional study was conducted on 183 tissue samples, including benign, borderline, and malignant ovarian tumors collected from the University Kebangsaan Malaysia Medical Center archive of Pathology during 2005-2015. Mouse monoclonal anti-human Endocan/ESM-1 Clone MEP08 was used at a dilution of 1:400 for immunohistochemical (IHC) staining. All the information was collected by a checklist, and the association between clinicopathological features and high or low levels of Endocan -MVD was evaluated using Pearson chi-square, Fischer's exact, or Monte Carlo tests.Results:The prevalence of Endocan positivity was significantly higher in malignant compared to borderline and benign ovarian tumors (P<0.001). There was also a significant association between type of tumor and Endocan status in malignant ovarian tumors (P=0.02), indicating that Endocan positivity was more likely in serous malignant ovarian tumors compared to other ovarian tumor types. However, the tumor stage was not significantly associated with Endocan status (P=0.31). Conclusion:This study showed that Endocan positivity may show the highest prevalence among malignant tumors suggesting that high Endocan expression would be negatively associated with ovarian tumor behavior.

Endocan, a Soluble Marker of Endothelial Cell Activation Is a Molecular Marker of Disease Severity in Women with Preeclampsia.

Endocan is a proteoglycan secreted by activated endothelium that regulates angiogenesis via interaction with hepatocyte growth factor (HGF). We hypothesized that women diagnosed with preeclampsia (PE) and/or fetal growth restriction (FGR) have elevated circulating endocan concentrations in direct relationship with severity of clinical manifestations. Serum concentration of endocan and HGF were analyzed in 224 women grouped as healthy pregnant controls (P-CRL, n = 77), PE with severe features (sPE, n = 83), chronic hypertension (crHTN: n = 36), idiopathic FGR (n = 18), and healthy non-pregnant controls (NP-CRL, n = 7). Endocan and HGF measured by immunoassay were analyzed along with markers of inflammation, angiogenesis, and protein misfolding (urine congophilia). Endocan expression in the placenta and/or myometrium was studied by immunohistochemistry and real-time PCR. Compared to gestational age-matched P-CRL, women with early-onset sPE had higher circulating endocan concentrations. Among women with PE and/or FGR, endocan concentration correlated with soluble endoglin and urine congophilia but not with HGF or markers of inflammation or angiogenesis. In the placenta, endocan was expressed in villous and extravillous trophoblasts and endothelium. Intense endocan immunostaining was observed in plaque-like aggregations of sPE placentas complicated with FGR. In addition, thickened blood vessels in the myometrium of sPE patients stained positive for endocan. Women with early-onset sPE have elevated serum endocan likely reflecting chronic endothelial activation. Enhanced expression and/or deposition of endocan at the sites of placental injury and in remodeled maternal blood vessels supports a role for endocan in either vascular rescue or as a contributor to FGR and perhaps long-term cardiovascular morbidity.

Endocan: A Key Player of Cardiovascular Disease.

Endothelial dysfunction is considered to be an early change in atherosclerosis. Endocan, also known as endothelial cell specific molecule-1, is a soluble proteoglycan mainly secreted by endothelial cells. Inflammatory factors such as IL-1β and TNF-α can up regulate the expression of endocan and then affect the expression of cell adhesion molecules, such as ICAM-1 and VCAM-1, which play an important role in promoting leukocyte migration and inflammatory response. Elevated plasma levels of endocan may reflect endothelial activation and dysfunction, and is considered to be a potential immuno-inflammatory marker that may be related to cardiovascular disease. In the case of hypertension, diabetes, angina pectoris and acute myocardial infarction, the increase or decrease of serum endocan levels is of great significance. Here, we reviewed the current research on endocan, and emphasis its possible clinical value as a prognostic marker of cardiovascular disease. Endocan may be a useful biomarker for the prognosis of cardiovascular disease, but more research is needed on its mechanism of action.

Polysaccharide from Spirulina platensis improves sepsis-induced acute lung injury by alleviating inflammatory response and down-regulating endocan expression in rats

To explore the favourable functions of polysaccharide from Spirulina platensis (PSP) on sepsis-originated acute lung injury, together with the corresponding mechanisms. 60 male SD rats were randomly separated into sham, sepsis, and sepsis+PSP group with 20 rats in each group. Sepsis rat model was constructed by cecal ligation and puncture (CLP). The mortality and sepsis-related symptoms were used to judge the model success. CLP successfully established the sepsis-caused acute lung injury rat model. In sepsis rats, systemic inflammation and pulmonary inflammation, as well as endocan protein level were increased. PSP treatment improved sepsis-induced acute lung injury and systemic inflammation, and reduced the endocan protein level. Lung injury biomarkers were positively correlated with serum pro-inflammatory factors/serum endocan protein, while serum pro-inflammatory factors were positively associated with serum endocan level. PSP ameliorates acute lung injury via relieving inflammatory response and down-regulating endocan expression in sepsis rat.

Association of endocan expression with clinicopathological prognostic parameters in breast carcinoma.

Breast cancer (BC) is a common malignancy in women. Some molecules, including endocan, are still under investigation as potential prognostic factors in BC. In the present study, we aimed to determine the relationship between endocan expression and clinicopathological prognostic parameters in BC. Two hundred and fifty-five patients diagnosed with BC were included in the present study. The immuno-reactivity scoring (IRS) system was used to reveal the tissue endocan expression levels. We found that endocan expression is associated with tumor necrosis, tumor size, and the presence of lobular carcinoma in situ (LCIS) in BC. There was no relationship between endocan expression and survival as well as other clinicopathological prognostic parameters. Endocan overexpression in BC is associated with some prognostic parameters, including tumor necrosis, tumor size, and the presence of LCIS. Further studies with larger series are needed to reveal the clinical and therapeutic implications of endocan in BC.

Expression of Endocan in Tissue Samples from Prostate Adenocarcinoma and Prostate Hyperplasia: A comparative retrospective study.

In this study, we aimed to determine whether there is a significant difference in endocan expression levels between prostate adenocarcinoma and prostate hyperplasia tissues by using an immunohistochemical method. Materials and Methods:All of 51 patients, who were getting treatment for the last 5 years, participated in the study. 31 of 51 patients underwent transrectal sonography (TRUSG) -assisted prostate biopsy because of prostate adenocarcinoma as diagnosed with elevated PSA levels and histopathological examination. The remaining 20 patients comprised the control group. The control group included patients with benign prostate hyperplasia based on pathological examination. Results:It was found that there was strong positive epithelial staining in 74.2% of patients with prostate cancer while in 5% of controls, indicating a statistically significant difference (P < .001). It was also found that the rate of strong positive endothelial staining was 77.4% in the patient group whereas 5% in the control group (P < .001). Also, the rate of strong positive stromal staining was 64.5% in the patient group while 5% in the control group (P < .001). Conclusion:We found that tissue endocan expression level was statistically significantly higher in patients with prostate cancer compared to those with benign prostate hyperplasia by using an immunohistochemical method.

Dengue Virus Induces the Expression and Release of Endocan from Endothelial Cells by an NS1-TLR4-Dependent Mechanism.

A common hallmark of dengue infections is the dysfunction of the vascular endothelium induced by different biological mechanisms. In this paper, we studied the role of recombinant NS1 proteins representing the four dengue serotypes, and their role in promoting the expression and release of endocan, which is a highly specific biomarker of endothelial cell activation. We evaluated mRNA expression and the levels of endocan protein in vitro following the stimulation of HUVEC and HMEC-1 cell lines with recombinant NS1 proteins. NS1 proteins increase endocan mRNA expression 48 h post-activation in both endothelial cell lines. Endocan mRNA expression levels were higher in HUVEC and HMEC-1 cells stimulated with NS1 proteins than in non-stimulated cells (p < 0.05). A two-fold to three-fold increase in endocan protein release was observed after the stimulation of HUVECs or HMEC-1 cells with NS1 proteins compared with that in non-stimulated cells (p < 0.05). The blockade of Toll-like receptor 4 (TLR-4) signaling on HMEC-1 cells with an antagonistic antibody prevented NS1-dependent endocan production. Dengue-infected patients showed elevated serum endocan levels (≥30 ng/mL) during early dengue infection. High endocan serum levels were associated with laboratory abnormalities, such as lymphopenia and thrombocytopenia, and are associated with the presence of NS1 in the serum.

Tumor necrosis factor alpha expression is increased in maternal microvascular endothelial cells in preeclampsia

ABSTRACT Objective: The aim of this study was to explore the expression and effects of tumor necrosis factor alpha (TNFα) in maternal endothelial cells in preeclampsia (PE). Methods: Expression levels in primary microvascular endothelial cells (MVEC) isolated from patients with severe preeclampsia (PE) and normal pregnancies were determined by RT-qPCR with or without treatment of TNFα and inhibitors for downstream signaling. Results: PE MVEC exhibited increased basal TNFα expression. TNFα treatment increased TNFα, VCAM, and endocan expression in MVEC. Conclusion: TNFα expression is increased in PE MVEC and the treatment of these cells with exogenous TNFα modifies their gene expression.