Are serum levels of ADAMTS5, TAS and TOS at 24-28 gestational weeks associated with adverse perinatal outcomes in gestational diabetic women?

We aimed to determine the role of placental A Disintegrin and Metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and maternal serum ADAMTS5, total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) levels at 24-28th gestational weeks in GDM. This study included 57 patients, who had been diagnosed as having GDM at their 24-28th gestational week, and 29 controls. The maternal blood samples were collected at the 24-28th gestational week and ADAMTS5 was studied with the enzyme-linked immunosorbent assay (ELISA) method, whereas an automated colorimetric method was used to study TAS, TOS, and OSI. The level of ADAMTS5 in maternal serum of patients with GDM were significantly lower than the controls (p = .017); whereas TOS and OSI levels were significantly higher (p = .003 and p = .008). Multivariable logistic regression analysis revealed ADAMTS5 and TOS levels were independently associated with adverse perinatal outcomes (p = .004 and p = .018). We found that serum ADAMTS5 levels decreased and TOS level increased in GDM pregnant at 24-28th gestational weeks. In addition, we found that increased levels of serum ADAMTS5 and decreased TOS levels at 24-28th weeks were associated with adverse perinatal outcomes independent of the mode of treatment in GDM.Impact statementWhat is already known on this subject? Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. The insulin resistance, which starts at the 24-28th gestational weeks, increases during gestation. GDM increases maternal complications like preeclampsia, cesarean rate, cardiovascular disease, obesity, and diabetes after pregnancy; and neonatal complications like macrosomia, hypoglycemia, hyperbilirubinemia, delivery trauma, shoulder dystocia, and adult-onset obesity, and diabetes.What the results of this study add? A significant relationship between ADAMTS5, TOS levels and adverse perinatal outcome. insulin resistance and was observed.What the implications are of these findings for clinical practice and/or further research? Based on this finding, we concluded that increased levels of oxidative stress and decreased ADAMTS5 levels are associated with GDM and predictive for adverse perinatal outcomes. The results of the present study were consistent with the previous reports and indicated that increased oxidative stress in GDM patients are related to adverse perinatal outcomes.

The investigation of serum levels of ADAMTS 5 and 8 (the A disintegrin and metalloproteinase with thrombospondin motifs) in the etiology of endometrial cancer.

The aim of this study was to investigate the serum levels of the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5 and 8 in patients diagnosed with endometrial cancer. Our study included 41 patients diagnosed with endometrial cancer. The control group consisted of 41 patients diagnosed with benign endometrial pathology. The serum samples were centrifuged and stored at -80 °C. The serum levels of ADAMTS were significantly higher (p<.001), whereas the levels of ADAMTS 8 were significantly lower in patients diagnosed with cancer (p<.001). In addition to the presence of known factors in the aetiology of endometrial cancer, the effect of inflammatory factors and some new proteins has centred on the causes of tumourigenesis in recent years. In this sense, these proteins, called the ADAMTS, are the source of new studies.Impact StatementWhat is already known on this subject? When the recent studies about endometrial cancer are evaluated, it is seen that the effects of chronic inflammation and cytokines have gained importance in its aetiology. The A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) gene family consist of 19 proteases that play essential role in the formation of the extracellular matrix (ECM) and interact with inflammatory cytokines. These proteases and their substrates provide a wide range of functions in different tissues, including ECM remodelling, angiogenesis, fibrosis and coagulation.What the results of this study add? ADAMTS 5, which causes the degradation of the ECM with Aggrecanase activity, was found to be significantly higher in patients diagnosed with cancer and ADAMTS 8 with anti-angiogenesis activity was significantly lower in patients diagnosed with endometrial cancer.What the implications are of these findings for clinical practice and/or further research? In this study, it is understood that the effect of inflammatory mediators is remarkably important in the aetiology of endometrial cancer, as in many types of organ specific cancer.

ADAMTS-5 Decreases in Coronary Arteries and Plasma from Patients with Coronary Artery Disease.

The current study demonstrates that a disintegrin and metalloproteinase with thrombospondin type 1 motif- (ADAMTS-) 5 is a key extracellular matrix protease and associated with cardiovascular diseases. However, the plasma ADAMTS-5 levels and relevance of coronary artery disease (CAD) remain largely unknown. This study is aimed at examining the relationship between the plasma ADAMTS-5 levels and the severity of coronary stenosis in patients with CAD. In the present study, the expression of ADAMTS-5 was analyzed in coronary artery samples and blood. The results showed that the plasma ADAMTS-5 levels were lower in the CAD group than in the control group. In addition, significantly higher matrix metalloproteinase- (MMP-) 2 and MMP-9 levels were also observed in the patients with CAD, and the ADAMTS-5 levels were negatively correlated with the MMP-2 and MMP-9 levels. Spearman's correlation analysis showed that the Gensini score was negatively correlated with the ADAMTS-5 levels but was positively correlated with the MMP-2 and MMP-9 levels. Receiver-operating characteristic (ROC) analysis revealed that ADAMTS-5, MMP-2, and MMP-9 may have a certain diagnostic value in CAD and that the combination of all three metalloproteinases had a higher diagnostic value. The findings provided a better understanding of the role of ADAMTS-5 in the diagnosis of CAD.

The role of novel cytokines in inflammation: Defining peripheral artery disease among patients with coronary artery disease.

Coronary artery disease (CAD) patients with concomitant peripheral artery disease (PAD) experience more extensive and calcified atherosclerosis, greater lesion progression and more common coronary events compared to patients with CAD only. To characterize the distinct features of this aggressive atherosclerotic disease, we studied novel cytokines that code different stages of atherogenesis. One hundred and eighty consecutive subjects (60 patients into each group of CAD+PAD, CAD and controls) were recruited among patients with stable angina pectoris scheduled for coronary angiography. An ankle-brachial index (ABI) ≤0.9 was determined as occlusive PAD. Fasting serum tumor necrosis factor (TNF)-like antigen 1A (TL1A) and its receptor death receptor 3 (DR3), NOGO-B (reticulon 4B) and its receptor NUS1, high-sensitivity C-reactive protein (hsCRP), A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 1, 4, 5 and interleukin (IL) 6 levels were determined. Serum hsCRP and DR3/TL1A concentrations were similar and higher than controls in the CAD and CAD+PAD groups. Levels of NOGO-B and its receptor NUS1 were increased and ADAMTS-5 was decreased in patients with CAD+PAD. Independent predictors of ABI in multivariate analysis were smoking (B = -0.13, p = 0.04), NUS1 (B = -0.88, p < 0.001), ADAMTS-5 (B = 0.63, p < 0.001) and SYNTAX score (B = -0.26, p < 0.001). Similarly, smoking (OR = 5.5, p = 0.019), SYNTAX score (OR = 1.2, p < 0.001), NUS1 (OR = 14.4, p < 0.001), ADAMTS-5 (OR = 1.1, p < 0.001) and age (OR = 1.1, p = 0.042) independently predicted the involvement of peripheral vasculature in logistic regression. The diagnostic performance of these cytokines to discriminate CAD+PAD were AUC 0.79 ( p < 0.001) for NUS1 and 0.37 ( p = 0.013) for ADAMTS-5. We report herein that circulating cytokines can give clues to the ongoing atherosclerotic process and the extent of vascular involvement in which distinct features of ADAMTS-5 and NUS1 make them promising cytokines for future research.

Clinical significance of ADAMTS1, ADAMTS5, ADAMTS9 aggrecanases and IL-17A, IL-23, IL-33 cytokines in polycystic ovary syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) are involved in inflammation and fertility. The aim of this investigation was to evaluate the serum levels of ADAMTS1, ADAMTS5, ADAMTS9, IL-17, IL-23, IL-33 and to find out the relationship between these inflammatory cytokines and ADAMTSs in PCOS patients. METHODS: A case-control study was performed in a training and research hospital. Eighty patients with PCOS and seventy-eight healthy female volunteers were recruited in the present study. Serum ADAMTS and IL levels were determined by a human enzyme-linked immunoassay (ELISA) in all subjects. RESULTS: The IL-17A, IL-23 and IL-33 levels were significantly higher in the PCOS patients compared to the controls (p < 0.05). We could not find significant difference between the groups in terms of ADAMTS1, ADAMTS5 and ADAMTS9 levels. IL-17A had positive correlations with LDL cholesterol and IL-33 and negative correlations with ADAMTS1, ADAMTS5, and ADAMTS9. IL-33 had positive correlation with LDL cholesterol and IL-17A. In ROC curve analysis, PCOS can be predicted by the use of IL-17A, IL-23 and IL-33 which at a cut-off value of 8.37 pg/mL (44 % sensitivity, 83 % specificity), 26.75 pg/mL (36 % sensitivity, 64 % specificity) and 14.28 pg/mL (83 % sensitivity, 39 % specificity), respectively. CONCLUSIONS: The results of the study might suggest that ADAMTS and IL molecules have a role in the pathogenesis of the PCOS. Further efforts are needed to establish causality for ADAMTS-IL axis.