Association Between Plasma ADAMTS-9 Levels and Severity of Coronary Artery Disease.

Genome-wide association studies have shown that a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS-9) is associated with the development of atherosclerosis. We assessed the level of ADAMTS-9 in patients with coronary artery disease (CAD) and its severity and prognosis. We selected 666 participants who underwent coronary angiography in our hospital and met the inclusion and exclusion criteria; participants included non-CAD patients, patients with stable angina pectoris (SAP), unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction. The serum level of ADAMTS-9 was higher in patients with CAD than in non-CAD patients (37.53 ± 8.55 ng/mL vs 12.04 ± 7.02 ng/mL, P < .001) and was an independent predictor for CAD (odds ratio = 1.871, 95% CI: 1.533-2.283, P < .001). Subgroup analysis showed that compared with the SAP group, the acute coronary syndrome groups had higher serum levels of ADAMTS-9. In addition, the level of ADAMTS-9 was related to the SYNTAX score (r = 0.523, P < .001). Patients with acute myocardial infarction (AMI) with elevated levels of ADAMTS-9 had a higher risk of major adverse cardiovascular events (MACE) within 12 months than those with lower levels (log-rank = 4.490, P = .034). Plasma ADAMTS-9 levels may be useful for the diagnosis of CAD and as predictors of MACE in AMI patients.

Decreased ADAMTS-1, -9 and -20 levels in women with endometrial polyps: a possible link between extracellular matrix proteases and endometrial pathologies.

A disintegrin-like and metalloproteinase domain with thrombospondin-type 1 motifs (ADAMTS) protein superfamily includes 19 secreted metalloproteases. Proteolytic substrates of ADAMTS enzymes have been linked to female reproductive function. Herein, we aimed to investigate serum ADAMTS-1, -9 and -20 levels in women with and without endometrial polyps (EPs). The study group (n = 40) consisted of women who had hysteroscopically detected and histologically confirmed EPs whereas control group (n = 40) was recruited from those women without any endometrial pathology. Data recorded for every woman were as follows: age, body mass index, gravidity and parity, number of miscarriages, smoking status and serum ADAMTS-1, -9 and -20 levels. ADAMTS-1, -9 and -20 values were measured by commercially available ELISA kits. No statistically significant differences between the groups were observed in terms of demographics. There were also no statistically significant differences between the groups with regard to ADAMTS-1 and -20 levels, although both of them were lower in the study group. However, ADAMTS-9 was significantly lower in the study group compared to the controls (p = .010). The optimal cut off value of ADAMTS-9 in predicting EPs was found to be 163.2 ng/mL with 100% sensitivity and 35% specificity. In conclusion, ADAMTS-9 protein is decreased in women with EPs. Impact statement What is already known on this subject? Endometrial polyps (EPs) are common and are generally benign gynaecologic disorders. ADAMTS enzymes comprise a zinc metalloproteinase gene family that has roles in vascular biology, inflammation and especially in the control of the function and structure of the extracellular matrix (ECM). ECM plays an important role in the pathogenesis of myomas, adenomyosis and abnormal uterine bleeding, as well as EPs. There is an interest in these proteases, especially with regard to the physiology of ovulation and implantation. They are also associated with carcinogenesis and metastasis. One of the most feared consequences of EPs is the risk of malignancy. Therefore, it is important in gynaecology practice to diagnose these endometrial abnormalities. What do the results of this study add? This is the first study performed to investigate the relationship between some ADAMTS (-1, -9 and -20) proteases and uterine polyps. Our results demonstrate novel molecular mediators contributing to EPs physiopathology. What are the implications of these findings for clinical practice and/or further research? ADAMTS-9 is defined as a tumour suppressor gene in various malignancies. Decreased ADAMTS-9 protein, which is the product of this gene, may have a role in the pathogenesis of EPs. There is a need for further research that should be done with benign-malign EPs.

The role of ADAMTS4 and ADAMTS9 in cardiovascular disease in premature ovarian insufficiency and idiopathic hypogonadotropic hypogonadism.

PURPOSE: We aimed to determine the relation of a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4), and a disintegrin and metalloproteinase with thrombospondin motifs-9 (ADAMTS9) with cardiovascular disease (CVD) risk, in ovarian dysfunction patients with premature ovarian insufficiency (POI), and idiopathic hypogonadotropic hypogonadism (IHH). METHODS: 43 IHH and 44 POI patients were enrolled to this case-control study. Serum hormonal parameters, lipid profiles, ADAMTS4 and ADAMTS9 levels were measured. Lipid accumulation product (LAP) index, visceral adiposity index (VAI), and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. The patients with at least two out of the four following criteria were accepted to have increased CVD risk; waist-to-hip ratio (WHR) ≥ 0.8, waist circumference (WC) ≥ 79 cm, triglycerides (TG) ≥ 150 mg/dL, high-density lipoprotein cholesterol (HDL-C) < 50 mg/dL. Serum ADAMTS4 and ADAMTS9 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: ADAMTS4 and ADAMTS9 levels were significantly higher in the IHH group than the POI group (p = 0.002, and p = 0.013, respectively). IHH group had significantly higher levels of insulin, HOMA-IR index, and LAP index (p = 0.006, p = 0.005, and p = 0.013, respectively). The mean age of patients in the IHH group (23.60 ± 5.64 years) was significantly lower than the POI group (31.05 ± 6.03 years), (p < 0.001). Odds ratios (OR) were 1.236 (95% CI 1.055-1.447) and 1.002 (95% CI 1.000-1.004) for LAP index and ADAMTS4, respectively, in the IHH group. These two parameters found to have high predictivity for CVD risk in the IHH group (p = 0.009 and p = 0.028, respectively). CONCLUSION: The lower levels of ADAMTS4 in the POI group, when compared with the IHH patients pointed out that even limited hormone secretion and ovulation in the POI group, may have protective effect on cardiovascular system. The higher levels of ADAMTS4 and LAP index in the IHH group demonstrated the increased risk of these patients for CVD.

Association of ADAMTS4 and ADAMTS9 levels with cardiovascular risk in patients with primary hyperparathyroidism.

PURPOSE: Primary hyperparathyroidism (PHPT) has been associated with increased incidence of morbidity and mortality of the cardiovascular system. The pathogenetic mechanisms underlying this association are still not completely clear. A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) play a critical role in atherosclerosis. This study aimed to investigate the levels of ADAMTS4 and ADAMTS9 and relationship between these proteoglycanases and cardiometabolic abnormalities in PHPT. MATERIALS AND METHODS: A case-control study was performed in a training and research hospital. Fifty-six patients with PHPT and 61 healthy volunteers were recruited. The Framingham score was used to calculate cardiovascular risk (CVR). Serum ADAMTS levels were determined by a human enzyme-linked immunoassay in all subjects. RESULTS: The ADAMTS9 concentration was significantly higher in patients with PHPT than in the control group (p < 0.05); however, there were no significant differences in ADAMTS4 levels between the groups (p > 0.05). In ROC curve analysis, PHPT can be predicted by the use of ADAMTS9 at a cut-off value of 30.7 pg/mL (69% sensitivity, 65% specificity). CVR score was significantly increased in the PHPT than controls (p < 0.05). ADAMTS4 and ADAMTS9 levels had positive correlations with CVR score (r = 0.322, p = 0.017; r = 0.275, p = 0.044 respectively). CONCLUSIONS: Based on the results of the present study, cardiovascular risk is increased in PHPT and associated with ADAMTS4 and ADAMTS9. Further efforts are needed to establish the function of ADAMTS proteases in both PHPT and atherosclerosis.

Maternal serum ADAMTS-9 levels in gestational diabetes: a pilot study.

OBJECTIVE: Gestational diabetes mellitus (GDM) is characterized with insulin resistance which is diagnosed during pregnancy. Although pregnancy is a diabetogenic state, not all women develop GDM. Genetic factors together with enviromental factors cause the maladaptation of maternal pancreas to this diabetogenic state and GDM develops. ADAMTS-9 is a recently recognized molecule whose genetic variants have risk of GDM. Decreased levels have already been shown in fetal membranes. Maternal serum levels of this protein have not been studied yet. We hypothesized that the alteration of ADAMTS-9 expression should cause changes in maternal serum levels which further could help to identify the disease and develop new treatment strategies. MATERIALS AND METHODS: This prospective case-control study is consisted of 27 pregnancies with GDM and 30 healthy singleton pregnancies matched for matenal age, gestational week, and maternal weight. GDM diagnosis was made with 2-h 75 g oral glucose tolerance test. ADAMTS-9 levels were compared between groups. RESULTS: ADAMTS levels were 3.62 ± 0.33 ng/dL (range: 3.04-4.23) in GDM group and 4.65 ± 1.70 ng/dL (range: 3.07-8.21) in control group (p < 0.001). ADAMTS levels were not affected by maternal age, gestational age, and maternal weight. CONCLUSION: ADAMTS-9 levels were significantly lower in GDM pregnancies. This may help to understand the mechanism of GDM pathogenesis. In future, target treatments with ADAMTS proteins may help to improve the severity of diabetes pathogenesis.

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.