Dermatan Sulfate Proteoglycan Research Articles

Serum endocan as a predictive biomarker of cardiovascular risk in obese pediatric patients

BackgroundEndocan is a soluble dermatan sulfate proteoglycan (50 kDa) secreted by endothelial cells and expressed by dermal, coronary, pulmonary and adipose tissue microvasculature. It plays an important role in the pathogenesis of vascular disorders, inflammatory state, endothelium dysfunction and neoangiogenesis. Aims of the study were to compare fasting serum endocan levels between children with obesity and healthy controls and to investigate the relationships between endocan, body mass index (BMI) and other indices of cardiometabolic risk.MethodsThis single-center, observational, retrospective study included 19 pediatric patients with obesity aged 11.94 ± 0.52 years and 19 lean matched controls. Each patient underwent clinical and auxological examination and laboratory investigations including routine organs function tests and lipid profile. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Fasting endocan serum levels were measured using an enzyme-linked immunosorbent assay (ELISA).ResultsCompared to healthy subjects, serum endocan levels were found to be significantly upraised in children with obesity. Endocan resulted significantly correlated with insulin levels (rho 0.47; p = 0.04); in addition, an association with HOMA-IR values with a trend toward the statistical significance (rho 0.43; p = 0.07) was found. No significant correlation with fasting blood glucose values and lipid serum levels was demonstrated. Although not statistically significant, a correlation between endocan and the presence and grading of liver steatosis on ultrasound (rho 0.51; p = 0.08 and rho 0.51; p = 0.08, respectively) was found.ConclusionsThese findings confirm the association between endothelial damage and insulin resistance in children with obesity. Endocan could be used as a biomarker of early endothelial dysfunction in children with obesity and could be a valid predictor of future cardiovascular risk in adulthood.

Endocan is a key player in cardiovascular disease: A review

In recent years, the attention of scientists has been actively focused on studying the role of endocan as a biological marker of endothelial dysfunction in cardiovascular diseases. Until recent years, endocan has been studied in acute kidney injury, chronic kidney disease, and renal replacement therapy. Endocan, formerly known as endothelial cell-specific molecule-1, is a soluble dermatan sulfate proteoglycan expressed and secreted into the circulation from endothelial cells. Currently available studies demonstrate the diagnostic and prognostic value of endocan evaluation in cardiovascular pathology. It is expected that further scientific and clinical studies will demonstrate the possibilities of using endocan as an additional laboratory tool for diagnosing and assessing the prognosis in patients with a cardiac profile. Drug regulation of endocan concentration and expression may be a promising target for the treatment of cardiac and vascular pathology.

The Role of Endocan in Cardiometabolic Disorders

Discovered two decades ago, endocan still represents an intriguing biomarker related to inflammation. Endocan is a soluble dermatan sulphate proteoglycan secreted by endothelial cells. Its expression is observed in tissues related to the enhanced proliferation, especially hepatocytes, lungs, kidneys, etc. Endocan has been investigated in many cardiometabolic disorders that are tightly connected with inflammation, such as type 2 diabetes mellitus, hypertension, atherosclerotic cardiovascular disease, kidney disease, obesity, polycystic ovary syndrome, metabolic syndrome, non-alcoholic fatty liver disease, etc. In this narrative, comprehensive review of the currently available literature, special attention will be paid to the role of endocan in the broad spectrum of cardiometabolic disorders. Since endocan has emerged as a novel endothelial dysfunction marker, the discovery of potential therapeutic strategies for patients with certain cardiometabolic risk factors would be of great importance to delay or even prevent the onset and progression of related complications, mainly cardiovascular.

Cadmium induces chondroitin sulfate synthase 1 via protein kinase Cα and elongates chondroitin/dermatan sulfate chains in cultured vascular endothelial cells.

Cadmium is an environmental pollutant and a risk factor for atherosclerosis. In the atherosclerotic intima, dermatan sulfate chains accelerate accumulation and oxidation of LDL cholesterol. The major type of dermatan sulfate proteoglycan that is synthesized by vascular endothelial cells is biglycan. In the present study, we analyzed the effect of cadmium on the biglycan synthesis using cultured bovine aortic endothelial cells. Cadmium did not induce biglycan mRNA and core protein expression; however, it elongated the chondroitin/dermatan sulfate chains of biglycan. Among elongation enzymes of the chondroitin/dermatan sulfate chain, chondroitin sulfate synthase 1 (CHSY1) mRNA and protein expression were dose- and time-dependently upregulated by cadmium depending on protein kinase Cα. This finding suggests that CHSY1-dependent elongation of chondroitin/dermatan sulfate chains of biglycan may exacerbate cadmium-induced atherosclerosis.

Research progress on the role of endothelial cell-specific molecular-1 in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS), a common respiratory critical illness with multiple causes, is associated with high mortality. The high degree of heterogeneity may be the reason why it is lack of highly specific and sensitive biological biomarkers. Therefore, it is an urgent need to explore biomarkers, perform phenotypic analysis and establish risk stratification model for diagnosis, prognosis, and treatment of ARDS. Endothelial cells specificity molecular-1 (ESM-1, endocan), is a soluble dermatan sulfate proteoglycan, and be involved in regulating biological behaviors such as cell proliferation, differentiation and migration. Numerous studies have confirmed that ESM-1 is closely related to inflammation, endothelial activation and dysfunction. However, the role of ESM-1 in the initiating and developing process of ARDS is still unclear. To provide a scientific basis for its clinical applications in ARDS, such as early prognosis assessment and timely prevent strategies, this paper focuses on the biological properties and the clinical value of ESM-1 as a potential biomarker for ARDS.

1339-P: Plasma Heparin Cofactor II Activity Is Inversely Associated with the Development NAFLD in Patients with Diabetes

Aims and Introduction: The prevalence and incidence of nonalcoholic fatty liver disease (NAFLD) have been increasing worldwide. Thrombin exerts various pathophysiological functions via activation of protease-activated receptors (PARs) , and activation of PARs promotes the development of NAFLD. Since heparin cofactor II (HCII) specifically inhibits thrombin action by binding to dermatan sulfate proteoglycans in various tissue matrices, we hypothesized that plasma HCII activity is associated with the development of NAFLD. Materials and Methods: Plasma HCII activity and clinical markers for assessment of hepatic fibrosis including Fibrosis 4 (FIB-4) index, NAFLD fibrosis score (NFS) , and aspartate aminotransferase to platelet ratio index (APRI) were determined in 322 Japanese patients with diabetes mellitus (183 males and 139 females; mean age, 66.0±11.3 years) . The relationships between plasma HCII activities and the clinical markers were statistically evaluated. Results: The mean plasma HCII activity in all participants was 94.0 ± 17.7%. Multivariate regression analysis with adjustments for confounding factors including age, sex, and serum albumin showed that plasma HCII activity independently contributed to reduction of the FIB-4 index (p < 0.0001) , NFS (p < 0.0001) , and APRI (p < 0.05) . Conclusions: Plasma HCII activity was independently and inversely associated with the clinical markers of hepatic fibrosis. The results suggest that HCII can serve as a novel therapeutic target for the development of NAFLD in patients with diabetes. Disclosure T.Hara: None. I.Endo: None. M.Matsuhisa: Research Support; Nissui , Sysmex Corp., Speaker’s Bureau; Astellas Pharma Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. M.Abe: None. K.Aihara: None. H.Yamagami: None. S.Masuda: None. Y.Mitsui: None. K.Kurahashi: None. S.Yoshida: None. T.Otoda: None. T.Yuasa: None. A.Kuroda: None.

Endocan in Acute Leukemia: Current Knowledge and Future Perspectives.

Endocan is a soluble dermatan sulfate proteoglycan expressed by endothelial cells and detected in serum/plasma. Its expression is increased in tumors/tumor vessels in several human malignancies, and high expression (high serum/plasma levels or tumor levels) has an adverse prognostic impact in several malignancies. The p14 endocan degradation product can also be detected in serum/plasma, but previous clinical studies as well as previously unpublished results presented in this review suggest that endocan and p14 endocan fragment levels reflect different biological characteristics, and the endocan levels seem to reflect the disease heterogeneity in acute leukemia better than the p14 fragment levels. Furthermore, decreased systemic endocan levels in previously immunocompetent sepsis patients are associated with later severe respiratory complications, but it is not known whether this is true also for immunocompromised acute leukemia patients. Finally, endocan is associated with increased early nonrelapse mortality in (acute leukemia) patients receiving allogeneic stem cell transplantation, and this adverse prognostic impact seems to be independent of the adverse impact of excessive fluid overload. Systemic endocan levels may also become important to predict cytokine release syndrome after immunotherapy/haploidentical transplantation, and in the long-term follow-up of acute leukemia survivors with regard to cardiovascular risk. Therapeutic targeting of endocan is now possible, and the possible role of endocan in acute leukemia should be further investigated to clarify whether the therapeutic strategy should also be considered.

POS-675 DECORIN DEFICIENCY EXACERBATES PERITONEAL INFLAMMATION AND FIBROSIS IN A MURINE MODEL OF PERITONEAL DIALYSIS

Peritoneal dialysis (PD) is an important mode of renal replacement therapy, but its success depends on preservation of the structural and functional integrity of the peritoneal membrane. Despite being a common complication in patients on long-term PD, there is no effective treatment for peritoneal fibrosis. Decorin is a soluble dermatan sulphate proteoglycan, with anti-fibrotic properties, synthesized by peritoneal mesothelial cells. We previously demonstrated that decorin level in effluent dialysate decreased with increasing PD duration.

Neural Tissue Homeostasis and Repair Is Regulated via CS and DS Proteoglycan Motifs.

Chondroitin sulfate (CS) is the most abundant and widely distributed glycosaminoglycan (GAG) in the human body. As a component of proteoglycans (PGs) it has numerous roles in matrix stabilization and cellular regulation. This chapter highlights the roles of CS and CS-PGs in the central and peripheral nervous systems (CNS/PNS). CS has specific cell regulatory roles that control tissue function and homeostasis. The CNS/PNS contains a diverse range of CS-PGs which direct the development of embryonic neural axonal networks, and the responses of neural cell populations in mature tissues to traumatic injury. Following brain trauma and spinal cord injury, a stabilizing CS-PG-rich scar tissue is laid down at the defect site to protect neural tissues, which are amongst the softest tissues of the human body. Unfortunately, the CS concentrated in gliotic scars also inhibits neural outgrowth and functional recovery. CS has well known inhibitory properties over neural behavior, and animal models of CNS/PNS injury have demonstrated that selective degradation of CS using chondroitinase improves neuronal functional recovery. CS-PGs are present diffusely in the CNS but also form denser regions of extracellular matrix termed perineuronal nets which surround neurons. Hyaluronan is immobilized in hyalectan CS-PG aggregates in these perineural structures, which provide neural protection, synapse, and neural plasticity, and have roles in memory and cognitive learning. Despite the generally inhibitory cues delivered by CS-A and CS-C, some CS-PGs containing highly charged CS disaccharides (CS-D, CS-E) or dermatan sulfate (DS) disaccharides that promote neural outgrowth and functional recovery. CS/DS thus has varied cell regulatory properties and structural ECM supportive roles in the CNS/PNS depending on the glycoform present and its location in tissue niches and specific cellular contexts. Studies on the fruit fly, Drosophila melanogaster and the nematode Caenorhabditis elegans have provided insightful information on neural interconnectivity and the role of the ECM and its PGs in neural development and in tissue morphogenesis in a whole organism environment.

Anti-fibrotic effect of adipose-derived mesenchymal stem cell conditioned medium in muscle fibrosis.

Recent investigations have demonstrated that the administration of MSC in mouse model of diseases provided beneficial effects. On the other hand, human adipose-derived MSC condition medium (ADSC-CM) is reported as containing beneficial secreted factors, but its role in muscle fibrosis has not been identified. The aim of this study was to investigate the inhibitory effects of MSC-CM in muscle fibrosis in vitro using the C2C12 murine muscle, myoblast cell line. C2C12 cells were cultured overnight in 0.1% albumin-Dulbecco's Modifies Eagle's Medium (DMEM). The cells were then pre-incubated in ADSC-CM for 20 min, treated with 2.5-10 ng/mL human TGFβ1 for 8-72 hours and analyzed using RT-qPCR, Western blot and immunofluorescent staining. Treatment with 20% ADSC-CM for 3 days suppressed αSMA protein expression in TGFβ1 treated C2C12 cells. ADSC-CM stimulated the proliferation of C2C12 cells in a dose-dependent manner. Furthermore, TGFβ1 induced Acta2/αSMA mRNA expression which was inhibited by ADSC-CM treatment for 8 hours. Decorin, one of the dermatan sulfate proteoglycans and an endogenous inhibitor of TGFβ1, was expressed in ADSC-CM, but not in TGFβ1 pre-incubated ADSC-CM. Our studies provide useful information for establishing anti-fibrotic mechanism(s) of ADSC-CM, thus facilitating potential application to prevent muscle fibrosis.

Targeting Endothelial Cell-Specific Molecule 1 Protein in Cancer: A Promising Therapeutic Approach.

Despite the dramatic advances in cancer research in the past few years, effective therapeutic strategies are urgently needed. Endothelial cell-specific molecule 1 (ESM-1), a soluble dermatan sulfate proteoglycan, also known as endocan, serves as a diagnostic and prognostic indicator due to its aberrant expression under pathological conditions, including cancer, sepsis, kidney diseases, and cardiovascular disease. Significantly, ESM-1 can promote cancer progression and metastasis through the regulation of tumor cell proliferation, migration, invasion, and drug resistant. In addition, ESM-1 is involved in the tumor microenvironment, containing inflammation, angiogenesis, and lymph angiogenesis. This article reviews the molecular and biological characteristics of ESM-1 in cancer, the underlying mechanisms, the currently clinical and pre-clinical applications, and potential therapeutic strategies. Herein, we propose that ESM-1 is a new therapeutic target for cancer therapy.

Syndecan-1 downregulates syndecan-4 expression by suppressing the ERK1/2 and p38 MAPK signaling pathways in cultured vascular endothelial cells

Syndecan-1 and syndecan-4 are members of the syndecan family of transmembrane heparan sulfate proteoglycans. Vascular endothelial cells synthesize both species of proteoglycans and use them to regulate the blood coagulation-fibrinolytic system and their proliferation via their heparin-like activity and FGF-2 binding activity, respectively. However, little is known about the crosstalk between the expressions of the proteoglycan species. Previously, we reported that biglycan, a small leucine-rich dermatan sulfate proteoglycan, intensifies ALK5–Smad2/3 signaling by TGF-β1 and downregulates syndecan-4 expression in vascular endothelial cells. In the present study, we investigated the crosstalk between the expressions of syndecan-1 and other proteoglycan species (syndecan-4, perlecan, glypican-1, and biglycan) in bovine aortic endothelial cells in a culture system. These data suggested that syndecan-1 downregulated syndecan-4 expression by suppressing the endogenous FGF-2-dependent ERK1/2 pathway and FGF-2-independent p38 MAPK pathway in the cells. Moreover, this crosstalk was a one-way communication from syndecan-1 to syndecan-4, suggesting that syndecan-4 compensated for the reduced activity in the regulation of vascular endothelial cell functions caused by the decreased expression of syndecan-1 under certain conditions.

The significance of endocan immunohistochemical expression in chronic plaque psoriasis.

Psoriasis is a chronic inflammatory skin disease with immune-mediated mechanism. Endocan is a soluble dermatan sulfate proteoglycan expressed by endothelium of blood vessels. The present study aims to evaluate immunohistochemical localization of endocan in psoriatic skin in comparison with normal skin and to correlate its expression with the clinical and pathological data of psoriasis. Skin biopsies from 36 psoriatic patients and 40 normal subjects were taken and processed for immunohistochemical staining of endocan. Endocan was expressed in 63.9% and in 36.1% of epidermal keratinocytes and dermal endothelial and inflammatory cells of psoriatic skin, respectively, compared with its expression in 30% of epidermis of normal skin. Diffuse epidermal expression of endocan was in favor of cases with more angiogenesis and its intense expression was in favor of marked acanthosis and with cases affecting trunk as main presentation. Positive dermal endocan expression was significantly associated with marked parakeratosis and with more angiogenesis. Endocan is over-expressed in psoriatic skin from epidermal keratinocytes and dermal endothelial and inflammatory cells. Endocan enhances angiogenesis and proliferation of psoriatic skin contributing to pathogenic mechanisms of psoriasis.

A biphasic response of polymerized Type 1 collagen architectures to dermatan sulfate.

Collagen I, the most abundant extracellular matrix (ECM) protein in vertebrate tissues provides mechanical durability to tissue microenvironments and regulates cell function. Its fibrillogenesis in biological milieu is predominantly regulated by dermatan sulfate proteoglycans, proteins conjugated with iduronic acid-containing dermatan sulfate (DS) glycosaminoglycans (GAG). Although DS is known to regulate tissue function through its modulation of Coll I architecture, a precise understanding of the latter remains elusive. We investigated this problem by visualizing the fibrillar pattern of fixed Coll I gels polymerized in the presence of varying concentrations of DS using second harmonic generation microscopy. Measuring mean second harmonic generation signal (which estimates the ordering of the fibrils), and surface occupancy (which estimates the space occupied by fibrils) supported by confocal reflectance microscopy, our observations indicated that the effect on fibril pattern of DS is contextual upon the latter's concentrations: Lower levels of DS resulted in sparse disorganized fibrils; higher levels restore organization, with fibrils occupying greater space. An appropriate change in elasticity as a result of DS levels was also observed through atomic force microscopy. Examination of dye-based GAG staining and scanning electron microscopy suggested distinct constitutions of Coll I gels when polymerized with higher and lower levels of DS. We observed that adhesion of the invasive ovarian cancer cells SKOV3 decreased for lower DS levels but was partially restored at higher DS levels. Our study shows how the Coll I gel pattern-tuning of DS is of relevance for understanding its biomaterial applications and possibly, pathophysiological functions.

Higher serum Endocan levels are involved in the pathophysiology of chronic venous insufficiency

Aim: Chronic venous insufficiency (CVI) is a common but neglected pathology of the cardiovascular system with high diagnosis and treatment costs and negative effects on patients' quality of life. Endocan is a dermatan sulfate proteoglycan and secreted by activated vascular endothelium. We hypothesized that higher Endocan levels may be associated with the pathophysiology of CVI. Thus, in the current study, we aimed to assess the relationship between serum Endocan levels and CVI.
 Materials and Methods: Forty-four patients with CVI and 50 age- and gender- matched subjects were enrolled into the study. The baseline clinical characteristics of the patients were obtained and serum Endocan levels were calculated.
 Results: The mean Endocan level and mean triglyceride (TG) level were significantly higher in the CVI (+) group compared to the CVI (-) group (p

Endocan: A novel biomarker for risk stratification, prognosis and therapeutic monitoring in human cardiovascular and renal diseases

The vascular endothelium is localized at the interface between the blood and surrounding tissues, playing a pivotal role in the maintenance of tissue-fluid homeostasis and in the regulation of host defense, inflammation, vascular tone and remodeling, angiogenesis and haemostasis. The dysfunctional endothelium was shown to be implicated in the pathophysiology of several endothelial-dependent disorders, such as arterial hypertension, coronary artery disease, heart failure and chronic kidney disease, in which it is an early predictor of cardiovascular events.Endocan is a soluble dermatan sulphate proteoglycan mainly secreted by the activated endothelium. It is upregulated by several proinflammatory cytokines and proangiogenic factors and may itself contribute to the inflammatory status. In addition of being a surrogate marker of inflammation and endothelial dysfunction, it seems to be involved in the regulation of several proliferative and neovascularization processes. Therefore, its utility as a biomarker in a wide spectrum of diseases has been increasingly explored.Here, we review the current evidence concerning the role of endocan in several human cardiovascular and renal diseases, where it seems to be a promising biomarker for risk stratification, prognosis and therapeutic monitoring.

Dermatan sulfate epimerase 1 expression and mislocalization may interfere with dermatan sulfate synthesis and breast cancer cell growth

Dermatan sulfate (DS) is a glycosaminoglycan (GAG) that is produced through the epimerization of the glucuronic acid on chondroitin sulfate into iduronic acid (IduA) by dermatan sulfate epimerase (DS-epi) 1 and 2. Proteoglycans (PGs) play essential physiological and pathological roles during cellular development, proliferation, differentiation, and cancer metastasis. DS proteoglycans play vital roles during the process of tumorigenesis, due to the increased flexibility of the polysaccharide chain in the presence of IduA residues, which facilitate specific interactions with proteins, such as growth factors, cytokines, and angiogenic factors. Furthermore, DS-epi is highly expressed in many tumors, especially in esophageal squamous cell carcinoma. This study aimed to investigate the expression of DS-epi1 in multiple breast cancer cell lines, including MCF7 (luminal A), MDA-MB-231 (triple-negative) and SKBR3 (human epidermal growth factor receptor 2-positive), and its involvement in cancer progression. A SKBR3 variant, SKBR3m, presented the most erratic cell growth pattern when compared with those for MCF7 and MDA-MB-231. Moreover, SKBR3m cells demonstrated the highest level of DS-epi1 gene expression and higher 35S-DS content. However, at the protein level, MCF7 cells displayed the highest protein level for DS-epi1, whereas MDA-MB-231 cells had the lowest level. DS-epi1 was found in vesicles and in the perinuclear compartment only in SKBR3m cells, suggesting localization in the Golgi apparatus in these cells, in contrast with the cytoplasmic localization observed in MCF7 and MDA-MB-231 cells. The cytoplasm location of DS-epi1 likely compromised the formation of DS chains, but the core protein was detected using a decorin antibody. Golgi-specific labeling confirmed the localization of DS-epi1 in SKBR3m cells at the Golgi apparatus, indicating that the location of the enzyme was a determinant for the synthesis of DS in this cell line, suggesting that DS may play a decisive role in the tumor growth observed in this breast cancer cell line.

Koroner Kronik Total Oklüzyonu Olan Hastalarda Serum Endokan Düzeyi ile Koroner Kollateral Dolaşım Arasındaki İlişki

Introduction: Endocan, a dermatan sulfate proteoglycan, is synthesized and secreted by the vascular endothelium. It is involved in the pathogenesis of vascular diseases, organ-specific inflammations, and angiogenesis. The aim of the present study was to investigate the relationship between serum endocan level and development of coronary collateral circulation (CCC) in patients with stable angina pectoris. Patients and Methods: Patients with stable angina with at least one chronic total coronary occlusion (CTO) (n= 44) and who had normal coronary artery (n= 29) were included in the study. Collateral degree was evaluated according to the Rentrop and Cohen's classification. Patients who had grade 0 or 1 collateral filling were included in the poorly developed collateral group (n= 19), and those with grade 2 or 3 collateral filling were included in the well-developed collateral group (n= 23). Results: Endocan levels were significantly higher in patients in the well CCC group than in those in the poor CCC and control groups (p< 0.001). Endocan level is higher in patients with poorly developed CCC than in the control group. Endocan was only found as an independent predictor of well CCC in regression analysis (odds ratio 1.002, 95% confidence interval (CI) 1.001-1.005, p= 0.001). Receiver operating characteristic curve analysis detected an optimal cut-off value for endocan level of 1773.9 ng/L that predicted the presence of well development of CCC with a sensitivity of 84% and specificity of 63% (area under the receiver operating characteristic (ROC) curve: 0.749, 95% CI: 0.654-0.849, p< 0.001). Conclusion: Elevated endocan level is associated with better CCC in patients with CTO. Endocan may play an important role in the development of CCC.

Impaired Cognitive Function and Altered Hippocampal Synaptic Plasticity in Mice Lacking Dermatan Sulfotransferase Chst14/D4st1.

Chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans (PGs) are major extracellular matrix (ECM) components of the central nervous system (CNS). A large body of evidence has shown that CSPGs/DSPGs play critical roles in neuronal growth, axon guidance, and plasticity in the developing and mature CNS. It has been proposed that these PGs exert their function through specific interaction of CS/DS chains with its binding partners in a manner that depends on the sulfation patterns of CS/DS. It has been reported that dermatan 4-O-sulfotransferase-1 (Chst14/D4st1) specific for DS, but not chondroitin 4-O-sulfotransferase-1 (Chst11/C4st1) specific for CS, regulates proliferation and neurogenesis of neural stem cells (NSCs), indicating that CS and DS play distinct roles in the self-renewal and differentiation of NSCs. However, it remains unknown whether specific sulfation profiles of DS has any effect on CNS plasticity. In the present study, Chst14/D4st1-deficient (Chst14−/−) mice was employed to investigate the involvement of DS in synaptic plasticity. First, behavior study using Morris Water Maze (MWM) showed that the spatial learning and memory of Chst14−/− mice was impaired when compared to their wild type (WT) littermates. Corroborating the behavior result, long-term potentiation (LTP) at the hippocampal CA3-CA1 connection was reduced in Chst14−/− mice compared to the WT mice. Finally, the protein levels of N-Methyl-D-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, postsynaptic density 95 (PSD95), growth associated protein 43 (GAP-43), synaptophysin (SYN) and N-ethylmaleimide sensitive factor (NSF) which are important in synaptic plasticity were examined and Chst14/D4st1 deficiency was shown to significantly reduce the expression of these proteins in the hippocampus. Further studies revealed that Akt/mammalian target rapamycin (mTOR) pathway proteins, including protein kinase B (p-Akt), p-mTOR and p-S6, were significantly lower in Chst14−/− mice, which might contribute to the decreased protein expression. Together, this study reveals that specific sulfation of DS is critical in synaptic plasticity of the hippocampus and learning and memory, which might be associated with the changes in the expression of glutamate receptors and other synaptic proteins though Akt/mTOR pathway.

Serum endocan levels in patients with stable COPD.

BackgroundEndothelial cell specific molecule-1, also called as endocan, is a dermatan sulfate proteoglycan, which is expressed by endothelial cells in alveolar walls of the lung and kidney. High endocan levels are found associated with endothelial dysfunction and inflammation. We hypothesize that endocan level is also high in COPD due to systemic inflammation and endothelial dysfunction. We aimed to investigate the expression of endocan in patients with stable COPD.Material and methodsThe study included patients with COPD and control subjects. COPD patients were classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 criteria. Demographics, body mass index, smoking history, and comorbidities were recorded. Endocan levels of COPD patients and controls were compared.ResultsTotally, 88 subjects (47 stable COPD patients, 41 controls) were evaluated. Endocan levels were significantly higher in COPD patients than control group (860.1±259.8 vs 647.3±316.9 pg/mL, P=0.001). There was no relationship between GOLD COPD categories and endocan levels. Also endocan levels were similar between COPD patients with or without hypoxemia.ConclusionSerum endocan level was significantly higher in patients with stable COPD. Further studies should be performed to better understand the relationship between endocan and COPD.