Proinflammatory signaling mechanism of endocan in macrophages: Involvement of TLR2 mediated MAPK-NFkB pathways.

Endocan is an endothelial cell-specific proteoglycan that contributes to vascular dysfunction by impairing endothelial function and inducing vascular smooth muscle cell migration. However, its role in regulating macrophage inflammation, a key pathological feature of vascular dysfunction, is not well understood. In this study, we investigated the effect of endocan on macrophage inflammation to better understand its contribution to vascular dysfunction. We found that endocan upregulated pro-inflammatory cytokines including IL-1ß, IL-6 and TNF-α in RAW 264.7 cells and activated MAPK/NFkB signaling pathways. Inhibiting these pathways reduced endocan-induced cytokine levels, while inhibiting TLR2 compromised the MAPK/NFkB regulation. Additionally, LPS-induced HUVEC conditioned medium stimulated cytokine levels in RAW 264.7 cells, which were reduced by endocan siRNA treatment in HUVEC. These results suggest that endocan positively regulates pro-inflammation in macrophages through the TLR2-MAPK-NFkB axis, highlighting the potential of targeting endocan to reduce inflammation in vascular dysfunction.

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

BACKGROUND: 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. AIM: 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. METHODS: 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 3 mg/kg testosterone propionate per 2 days), (4) control + transfection (4 weeks after castration, injected with lentiviral vector (1 × 108 transduction units/mL, 10 µL), (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. OUTCOMES: 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. RESULTS: 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. CLINICAL IMPLICATIONS: Downregulating the expression of endocan in the penile corpus cavernosum may be a feasible approach for treating ED caused by hypoandrogenism. STRENGTHS AND LIMITATIONS: 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. CONCLUSION: 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.

The effect of supplemental oxygen and continuous positive airway pressure withdrawal on endocan levels.

PURPOSE: Endocan is a biomarker of endothelial dysfunction, which is a precursor to cardiovascular disease. Obstructive sleep apnoea (OSA) is associated with elevated endocan levels but the effects of treatment on endocan levels in OSA are not fully established. We aimed to determine whether endocan levels could be detected by immunoassay and to determine the effect of supplemental oxygen during continuous positive airway pressure (CPAP) withdrawal on circulating endocan levels. METHODS: We conducted an exploratory analysis from a randomised controlled crossover study which included participants with OSA. Participants stopped their CPAP therapy and were randomised to receive either supplemental oxygen or sham for 14 nights before crossing over. Supplemental oxygen blocked the rise in blood pressure seen in the sham group. We analysed plasma endocan levels by immunoassay at baseline and after 14 nights of intervention in both groups. RESULTS: Twenty-five participants were included, with a total of 100 samples. Endocan levels were detectable at all time points in 22 participants (88%), and in 93 (93%) samples. Supplemental oxygen had no effect on endocan levels compared to sham (+ 0.52 ng/ml, 95%CI -0.21 to + 1.25, p = 0.16), and there was no significant difference in endocan levels from baseline to follow-up in either the sham (-0.30 ng/ml, 95%CI -0.89 to + 0.30, p = 0.31) or supplemental oxygen (+ 0.22 ng/ml, 95%CI 0.00 to + 0.44, p = 0.05) arm. CONCLUSIONS: We have shown that endocan levels are detectable before and after CPAP withdrawal. However, we found no effect of supplemental oxygen following CPAP withdrawal on circulating endocan levels. TRIAL REGISTRATION AND DATE: ISRCTN 17,987,510 19/02/2015.

Investigation of Serum Endocan Levels in SARS-CoV-2 Patients.

Endocan is an endothelial-cell-specific proteoglycan (ESM-1) and has emerged as an endothelial dysfunction and inflammatory marker in recent years. Endocan can be used as a marker of inflammatory endothelial dysfunction in endothelium-dependent disease: cardiovascular disease, sepsis, lung and kidney disease and malignancies. Recent data suggest that endothelial dysfunction is a key mechanism in COVID-19 pathogenesis. Endotheliitis and thrombo-inflammation are associated with severe forms of SARS-CoV-2 infection, and endocan is currently under investigation as a potential diagnostic and prognostic marker. The aim of this study was to determine serum endocan levels in patients with COVID-19 to evaluate the correlation between endocan levels and clinical disease diagnosis and prognosis. This study enrolled 56 patients, divided into three groups depending on disease severity: mild (15), moderate (25) and severe (16). The biochemical, demographic, clinical and imagistic data were collected and evaluated in correlation with the endocan levels. Serum endocan levels were significantly higher in the COVID-19 patients compared to the control group; also, endocan concentration correlated with vaccination status. The results revealed significantly elevated serum endocan levels in COVID-19 patients compared to the control group, with a correlation observed between endocan concentration and vaccination status. These findings suggest that endocan may serve as a novel biomarker for detecting inflammation and endothelial dysfunction risk in COVID-19 patients. There was no significant relationship between serum endocan levels and disease severity or the presence of cardiovascular diseases. Endocan can be considered a novel biomarker for the detection of inflammation and endothelial dysfunction risk in COVID-19 patients.

Serum Endocan Is a Risk Factor for Aortic Stiffness in Patients Undergoing Maintenance Hemodialysis.

Background and Objectives: Endocan, secreted from the activated endothelium, is a key player in inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and angiogenesis. We aimed to investigate the link between endocan and aortic stiffness in maintenance hemodialysis (HD) patients. Materials and Methods: After recruiting HD patients from a medical center, their baseline characteristics, blood sample, and anthropometry were assessed and recorded. The serum endocan level was determined using an enzyme immunoassay kit, and carotid-femoral pulse wave velocity (cfPWV) measurement was used to evaluate aortic stiffness. Results: A total of 122 HD patients were enrolled. Aortic stiffness was diagnosed in 53 patients (43.4%), who were found to be older (p = 0.007) and have a higher prevalence of diabetes (p < 0.001) and hypertension (p = 0.030), higher systolic blood pressure (p = 0.011), and higher endocan levels (p < 0.001), when compared with their counterparts. On the multivariate logistic regression model, the development of aortic stiffness in patients on chronic HD was found to be associated with endocan [odds ratio (OR): 1.566, 95% confidence interval (CI): 1.224-2.002, p < 0.001], age (OR: 1.040, 95% CI: 1.001-1.080, p = 0.045), and diabetes (OR: 4.067, 95% CI: 1.532-10.798, p = 0.005), after proper adjustment for confounders (adopting diabetes, hypertension, age, systolic blood pressure, and endocan). The area under the receiver operating characteristic curve was 0.713 (95% CI: 0.620-0.806, p < 0.001) for predicting aortic stiffness by the serum endocan level, at an optimal cutoff value of 2.68 ng/mL (64.15% sensitivity, 69.57% specificity). Upon multivariate linear regression analysis, logarithmically transformed endocan was proven as an independent predictor of cfPWV (ß = 0.405, adjusted R2 change = 0.152; p < 0.001). Conclusions: The serum endocan level positively correlated with cfPWV and was an independent predictor of aortic stiffness in chronic HD patients.

Conventional and Novel Inflammatory Biomarkers in Chronic Heart Failure Patients with Atrial Fibrillation.

(1) Background and Objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity and mortality both in the general population and heart failure patients. Inflammation may promote the initiation, maintenance and perpetuation of AF, but the impact of inflammatory molecular signaling on the association between AF and heart failure remains elusive. (2) Materials and Methods: In 111 patients with chronic stable heart failure, baseline values of conventional (IL-6 and hsCRP) and selected novel inflammatory biomarkers (IL-10, IL-6/IL-10 ratio, orosomucoid and endocan) were determined. Inflammatory biomarkers were compared with respect to the presenting cardiac rhythm. (3) Results: Patients aged below 75 years with AF had significantly higher values of IL-6 and IL-6/IL-10 ratio; IL-6 levels were a significant predictor of AF in both univariate (OR 1.175; 95%CI 1.013-1.363; p = 0.034) and multivariate logistic regression analysis when accounting for other inflammatory biomarkers (OR 1.327; 95% CI 1.068-1.650; p = 0.011). Conversely, there was no association between other novel inflammatory biomarkers and AF. (4) Conclusions: IL-6 levels and the IL-6/IL-10 ratio are associated with AF in patients with chronic stable heart failure under the age of 75 years, suggesting that inflammatory molecular signaling may play a role in the development of AF in the heart failure population.

Can endocan serve as a molecular "hepatostat" in liver regeneration?

BACKGROUND: Intriguingly, 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. METHODS: Serum 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. RESULTS: Pcna 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. CONCLUSIONS: We 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.

Impact of early postoperative blood glucose variability on serum endocan level in cardiac surgery patients: a sub study of the ENDOLUNG observational study.

BACKGROUND: Early postoperative glycemic variability is associated with worse outcome after cardiac surgery, but the underlying mechanisms remain unknown. This study aimed to describe the relationship between postoperative glycemic variability and endothelial function, as assessed by serum endocan level in cardiac surgery patients. METHODS: We performed a post hoc analysis of patients included in the single-center observational ENDOLUNG study. Adult patients who underwent planned isolated coronary artery bypass graft surgery were eligible. Postoperative glycemic variability was assessed by calculating the coefficient of variability (CV) of blood glucose measured within 24 (CV24) and 48 (CV48) hours after surgery. Serum endocan level was measured at 24 (Endocan24) and 48 (Endocan48) hours after surgery. Pearson's correlation coefficient with 95% confidence interval (95% CI) was calculated between CV24 and Endocan24, and between CV48 and Endocan48. RESULTS: Data from 177 patients were analyzed. Median CV24 and CV48 were 18% (range 7 to 39%) and 20% (range 7 to 35%) respectively. Neither CV48 nor CV24 were significantly correlated to Endocan48 and Endocan24 respectively (r (95% CI) = 0.150 (0.001 to 0.290; and r (95% CI) = 0.080 (-0.070 to 0.220), respectively). CONCLUSIONS: Early postoperative glycemic variability within 48 h after planned cardiac surgery does not appear to be correlated with postoperative serum endocan level. CLINICAL TRIAL REGISTRATION NUMBER: NCT02542423.

Melatonin blunted the angiogenic activity in 3D colon cancer tumoroids by the reduction of endocan.

BACKGROUND: Complexity and heterogeneity of the tumor niche are closely associated with the failure of therapeutic protocols. Unfortunately, most data have been obtained from conventional 2D culture systems which are not completely comparable to in vivo microenvironments. Reconstructed 3D cultures composed of multiple cells are valid cell-based tumor models to recapitulate in vivo-like interaction between the cancer cells and stromal cells and the oncostatic properties of therapeutics. Here, we aimed to assess the tumoricidal properties of melatonin on close-to-real colon cancer tumoroids in in vitro conditions. METHODS: Using the hanging drop method, colon cancer tumoroids composed of three cell lines, including adenocarcinoma HT-29 cells, fibroblasts (HFFF2), and endothelial cells (HUVECs) at a ratio of 2: 1: 1, respectively were developed using 2.5% methylcellulose. Tumoroids were exposed to different concentrations of melatonin, from 0.005 to 0.8 mM and 4 to 10 mM, for 48 h. The survival rate was measured by MTT and LDH leakage assays. Protein levels of endocan and VEGF were assessed using western blotting. Using histological examination (H & E) staining, the integrity of cells within the tumoroid parenchyma was monitored. RESULTS: Despite the reduction of viability rate in lower doses, the structure of tumoroids remained unchanged. In contrast, treatment of tumoroids with higher doses of melatonin, 4 and 10 mM, led to disaggregation of cells and reduction of tumoroid diameter compared to the non-treated control tumoroids (p < 0.05). By increasing melatonin concentration from 4 to 10 mM, the number of necrotic cells increased. Data showed the significant suppression of endocan in melatonin-treated tumoroids related to the non-treated controls (p < 0.05). According to our data, melatonin in higher doses did not alter protein levels of VEGF (p > 0.05). CONCLUSIONS: Melatonin can exert its tumoricidal properties on colon cancer tumoroids via the reduction of tumor cell viability and inhibition of the specific pro-angiogenesis factor.

A novel inflammatory marker for extensive ulcerative colitis; Endocan.

BACKGROUND & AIMS: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by mucosal inflammation. Endocan, a proteoglycan secreted by endothelial cells in response to inflammatory cytokines, has been reported to be overexpressed in inflammatory conditions. In this study, we aimed to evaluate the utility of endocan level in determining the extent and severity of disease in patients with ulcerative colitis and to determine whether it can be a candidate marker for noninvasive evaluation and monitoring since there is not enough data in the literature. MATERIALS AND METHODS: Sixty-five people were included in the study, including thirty-five with ulcerative colitis and thirty in the control group. Patients with first diagnosed ulcerative colitis clinically, endoscopically, and histopathologically, without any treatment, and with normal liver and kidney tests were included in the study. Endoscopic scoring of all patients was performed according to the Mayo endoscopic scoring (MES) system. Blood samples for CRP (C-reactive protein) and endocan were taken from the patients simultaneously. RESULTS: There was a significant statistical difference between all patients with ulcerative colitis and the control group in both endocan level and CRP level (p < 0.001). There was a statistically significant difference between endocan levels and CRP levels between the left-distal group and pancolitis (diffuse colitis) patients, but there was no statistical difference between age and MES. CONCLUSION: Serum endocan level can be useful in determining the extent of ulcerative colitis and planning treatment.

Biomarkers of Glycocalyx Injury and Endothelial Activation are Associated with Clinical Outcomes in Patients with Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Sepsis is one of the main causes of morbidity and mortality worldwide. Microcirculatory impairment, especially damage to the endothelium and glycocalyx, is often not assessed. The objective of this systematic review and meta-analysis was to summarize the available evidence of the risk of unsatisfactory outcomes in patients with sepsis and elevated glycocalyx injury and endothelial activation biomarkers. DESIGN: A systematic search was carried out on PubMed/MEDLINE, Embase, Cochrane and Google Scholar up to December 31, 2021, including studies in adults and children with sepsis which measured glycocalyx injury and endothelial activation biomarkers within 48 hours of hospital admission. The primary outcome was the risk of mortality from all causes and the secondary outcomes were the risk of developing respiratory failure (RF) and multiple organ dysfunction syndrome (MODS) in patients with elevations of these biomarkers. MEASUREMENTS AND MAIN RESULTS: A total of 17 studies (3,529 patients) were included: 11 evaluated syndecan-1 (n=2,397) and 6 endocan (n=1,132). Syndecan-1 was higher in the group of patients who died than in those who survived [255 ng/mL (IQR: 139-305) vs. 83 ng/mL (IQR:40-111); p=0.014]. Patients with elevated syndecan-1 had a greater risk of death (OR 2.32; 95% CI 1.89, 3.10: p<0.001), MODS (OR 3.3; 95% CI 1.51, 7.25: p=0.003;), or RF (OR 7.53; 95% CI 1.86-30.45: p=0.005). Endocan was higher in patients who died [3.1 ng/mL (IQR 2.3, 3.7) vs. 1.62 ng/mL (IQR 1.2, 5.7); OR 9.53; 95% CI 3.34, 27.3; p<0.001], who had MODS (OR 8.33; 95% CI 2.07, 33.58; p=0.003) and who had RF (OR 9.66; 95% CI 2.26, 43.95; p=0.002). CONCLUSION: Patients with sepsis and abnormal glycocalyx injury and endothelial activation biomarkers have a greater risk of developing respiratory failure, multiple organ failure, and death. Microcirculatory impairment should be routinely evaluated in patients with sepsis, using biomarkers to stratify risk groups.

Evaluation of arterial stiffness and serum endocan levels in patients with primary aldosteronism with new-onset hypertension and long-term hypertension.

PURPOSE: There is growing evidence that prolonged exposure to high serum aldosterone concentrations results in target organ damage to the heart, kidney, and arterial wall, and that primary aldosteronism (PA) is associated with increased cardiovascular risk. In this study, we aimed to evaluate cardiovascular disease (CVD) risk indicators such as arterial stiffness [with pulse wave velocity (PWV) measurement] in PA patients and endocan levels, which is a biomarker of endothelial dysfunction. METHODS: 28 patients with PA were included in our study. As the control group, 14 patients with essential hypertension (EHT) and 28 normotensive healthy volunteers were included. Height, weight, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum fasting glucose, insulin, hemoglobin A1c (HbA1c), C-reactive protein (CRP), lipids and endocan levels of all subjects in the PA, EHT and control groups were measured. PWV measurements were performed to assess arterial stiffness. RESULTS: In the PA group, PWV levels were similar to the EHT group, and endocan levels were lower than the EHT group. In the PA group, PWV levels were higher than the control group, and endocan levels were lower than the control group. When we compared the PA group with new-onset HT with the PA group with long-term HT, PWV levels were higher in the PA group with long-term HT. When we compared the long-term HT group with the EHT group, PWV levels were higher in the long-term HT PA group and endocan levels were higher in the EHT group. When we compared the PA group with long-term HT with the control group, PWV levels were higher in the PA group with long-term HT, and endocan levels were similar in both groups. CONCLUSIONS: In our study, it was determined that arterial stiffness increased in PA cases with long-term HT compared to PA cases with new-onset HT, EHT cases and normotensive healthy cases. We found that endocan levels in PA patients were also lower than both EHT patients and healthy controls.

Is meteorin-like (Metrnl) a novel biomarker to distinguish patients with obstructive sleep apnea (OSA) and patients with OSA at vascular risk.

PURPOSE: Metrnl, a newly discovered adipokine with significant expression in white adipose tissue, promotes energy expenditure and contributes to the development of cardiovascular disorders. Endocan is a surrogate marker for endothelial dysfunction and is linked to cardiovascular risk factors. Higher cardiovascular morbidity and mortality have been linked to obstructive sleep apnea (OSA). In this study, we investigated the potential of serum Metrnl and endocan as biomarkers to identify patients with OSA who are at increased cardiovascular risk and differentiate them from healthy controls. METHODS: The study included the evaluation of serum levels of endocan and Metrnl in individuals with OSA and healthy controls. All participants underwent full polysomnography to evaluate their sleep, and carotid intima-media thickness (CIMT) was measured in each of them. RESULTS: Patients with OSA (n = 117) had considerably lower levels of Metrnl and significantly higher levels of endocan than controls (n = 59). Once confounding factors were taken into account, both Metrnl and endocan were effective predictors of OSA. Additionally, the severity of OSA, as determined by the apnea-hypopnea index (AHI), was linked to Metrnl and endocan levels. The study also found a significant and independent inverse association between CIMT and Metrnl, along with a positive association with endocan after making multiple adjustments. Furthermore, there was a significant and independent connection between CIMT and AHI. CONCLUSION: Based on these findings, Metrnl and endocan have the potential to be valuable markers for identifying patients with OSA who are at increased risk of early vascular damage.

Is maternal serum endocan level a novel marker in gestational diabetes mellitus?

AIM: To determine whether there was a significant difference between serum endocan levels of pregnant women with and without gestational diabetes mellitus (GDM). METHODS: A total of 90 pregnant women, 45 with gestational diabetes and 45 healthy pregnant women, between 24 and 28 gestational weeks, were included in this prospective case-control study. The pregnant women were screened for gestational diabetes using a two-step protocol. Serum endocan levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. A p-value of <0.05 was considered statistically significant. RESULTS: Serum endocan level was significantly higher in the GDM group than in healthy controls (168.46 ± 160.6 vs. 105.66 ± 26.52 pg/mL, respectively; p < 0.001). Serum endocan concentrations were positively correlated with the results of 50 g oral glucose challenge test (GCT) (p < 0.001). Receiver operating characteristic curve analysis showed that endocan with a cut-off point of 133.9 ng/dL indicated women with GDM with a sensitivity of 55.6% and specificity of 88.9% (area under the curve [AUC]: 0.737, 95% CI: 0.634-0.824). The overall differential performance of endocan according to the GDM groups was determined as 73.7% (p < 0.001). Maternal serum endocan level was positively correlated with fasting glucose, postprandial glucose, and glycated hemoglobin (HbA1c) (p < 0.001). CONCLUSIONS: Elevated endocan levels in gestational diabetes were correlated with fasting glucose, postprandial glucose, HbA1c, and oral glucose tolerance test (OGTT) results. Despite the low sensitivity of 55.6% and the high specificity of 88.9%, we found a high differential performance rate indicating that serum endocan levels were important for the pathophysiology of GDM and should be investigated for the possibility of being a novel marker in larger populations.

Serum endocan levels in patients with habitual abortion.

AIM: The aim of this study was to investigate whether there is a new factor in the etiology of recurrent loss of pregnancy. For this purpose, serum malondialdehyde (MDA) and nitric oxide (NO) levels as indicators of oxidative stress, and endocan levels, a marker of vascular dysfunction, were investigated in patients diagnosed with habitual abortion. MATERIALS AND METHODS: The research was conducted as a prospective case-control study. Patients aged 18-40 years with two or more consecutive pregnancy losses revealed by ultrasonographic or histopathological examination, and with no pathology capable of causing habitual abortion were included in the study group. Patients with no history of abortion, with at least one healthy pregnancy, who were planning pregnancies, and who presented to the outpatient clinic for routine prepregnancy tests were selected as the control group. Two groups were established-habitual abortion (n = 30) and control (n = 29). At the end of the menstrual cycle, blood samples were collected and centrifuged. Serum NO, MDA, and endocan levels were studied. RESULTS: Serum endocan, NO, and MDA levels were higher in women with habitual abortion compared to healthy controls. Pearson's correlation analysis revealed a positive correlation between serum endocan levels and NO and MDA levels. A positive correlation was also observed between serum MDA and NO levels. Multiple regression was run to predict serum endocan levels from MDA and NO levels. These variables emerged as statistically significant predictors of endocan. CONCLUSION: These findings suggest the presence of vascular endothelial dysfunction in patients with habitual abortion.

Serum endocan levels in children with rheumatic aortic insufficiency: can it differentiate bicuspid aortic valve disease from rheumatic heart disease?

AIM: In this study, it was aimed to examine the serum endocan levels in patients with rheumatic aortic regurgitation and to investigate whether it has a value in differentiating it from aortic regurgitation due to bicuspid aortic valve. METHODS: Blood samples were collected from patients with rheumatic aortic regurgitation (Group 1), incidentally diagnosed patients with borderline or definite rheumatic aortic regurgitation (Group 2), children with bicuspid aortic valve accompanied by aortic regurgitation (Group 3) and healthy children (Group 4) of similar age. RESULTS: There were 12 children in Group 1, 13 in Group 2, 25 in Group 3, and 25 in Group 4. Groups were similar in terms of age (p = 0.291). There was no statistically significant difference between median serum endocan levels of Group 1 and Group 2 (p = 0.624), and Group 3 and Group 4 (p = 0.443). Despite that, the median serum endocan levels of Group 1 and Group 2 were significantly higher than that of both Group 3 and Group 4 (p = 0.000 for all). CONCLUSIONS: Our results indicate that serum endocan level can be used to differentiate rheumatic aortic regurgitation from non-rheumatic aortic regurgitation. It is thought that the prognostic role of this marker should be confirmed in long-term, prospective studies with larger samples.

Investigation of Serum Endocan Levels and Age in Critical Inflammatory Conditions.

Aging negatively affects the endothelium. Endocan (ESM-1), an endothelium-derived soluble proteoglycan, participates in fundamental biological processes of endothelial cells. We aimed to examine the role of endothelial dysfunction and age in poor outcomes in critical illness. ESM-1 levels were measured in the sera of mechanically ventilated critically ill patients, including COVID-19, non-septic, and septic patients. The 3 patient cohorts were divided based on age (≥65 and <65). Critically ill COVID-19 patients had statistically higher ESM-1 levels compared to critically ill septic and non-septic patients. Only in critically ill septic patients were ESM-1 levels higher in older compared to younger patients. Finally, the age-subgrouped patients were further subdivided based on intensive care unit (ICU) outcome. ESM-1 levels were similar in COVID-19 survivors and non-survivors, irrespective of age. Interestingly, only for the younger critically ill septic patients, non-survivors had higher ESM-1 levels compared to survivors. In the non-septic survivors and non-survivors, ESM-1 levels remained unaltered in the younger patients and tended to be higher in the elderly. Even though endocan has been recognized as an important prognostic biomarker in critically ill patients with sepsis, in our patient cohort, increased age, as well as the extent of endothelial dysfunction, seemed to affect its prognostic ability.

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.