ADAMTS-3, -13, -16, and -19 levels in patients with habitual abortion.

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 reproductive function. The aim of this study was to investigate serum ADAMTS-3, -13, -16, and -19 levels in women with habitual abortions compared with those in healthy controls. A total of 86 women were enrolled in this prospective case-control study. ADAMTS-3, -13, -16, and -19 values were recorded and analyzed in association with demographic and clinical parameters. There were no statistically significant differences between the two groups in terms of demographics. No statistically significant differences were observed between the groups with regard to ADAMTS-13 and -19 levels (p>0.05). However, ADAMTS-3 and -16 were significantly higher in the study group than in the control group (p=0.004 and p=0.005, respectively). To estimate habitual abortions using an area under receiver operating characteristic curve analysis, the cutoff values for ADAMTS-3 and -16 were found to be 87.28 ng/mL (sensitivity, 64.44%; specificity 68.29%) and 15.75 ng/mL (sensitivity, 66.67%; specificity 68.29%), respectively. In conclusion, the pregnancy-loss rate seems to be affected by both ADAMTS-3 and -16.

A novel association between TGFb1 and ADAMTS4 in coronary artery disease: A new potential mechanism in the progression of atherosclerosis and diabetes.

OBJECTIVE: Coronary artery disease is characterized by atherosclerosis in the vessel wall. Recently, it has been thought that increasing LDL-binding capacity of subendothelial proteoglycan fragments that are formed by protease activity can be responsible for the initiation of atherosclerosis. ADAMTS4 is a member of the versican-degrading proteinases. In vitro studies demonstrated that TGFb inhibits the expression of ADAMTS4 in macrophages. In this study, we aimed to investigate the role and association between TGFb1 and ADAMTS4 in coronary artery disease. METHODS: A total of 84 cases with atheroma plaque and 72 controls without plaque were analyzed. The severity of disease was determined by Gensini score. TGFb1 gene polymorphisms were genotyped by the PCR-RFLP method. TGFb1 and ADAMTS4 serum levels were measured by ELISA method. Statistical analyses of genotypes and their relationship with serum levels were performed by chi-square, student t test and ANOVA. RESULTS: ADAMTS4 levels were higher in cases compared with controls (p<0.05). In the patient group, ADAMTS4 levels were higher than in controls and correlated with TGFb1 serum levels (r=0.29; p<0.05) and severity of disease (r=0.20; p<0.05). The TGFb1 gene CCA haplotype was associated with 3.3-fold increase in coronary artery disease (OR=3.26 95% CI 1.22-8.68; p<0.05). Unexpectedly, ADAMTS4 serum levels were also higher in diabetic cases (p=0.05). CONCLUSION: This study has demonstrated that ADAMTS4 may be responsible for the pathogenesis of atherosclerosis. This is the first report about the association between ADAMTS4 and TGFb1 serum levels in the progression of atherosclerosis in CAD. Furthermore, it is seen that TGFb1 haplotype can cause a genetic susceptibility to CAD in the Turkish population. To our knowledge, this is also the first report suggesting higher serum ADAMTS4 levels in diabetic patients.

Increased serum ADAMTS-4 in knee osteoarthritis: a potential indicator for the diagnosis of osteoarthritis in early stages.

We compared serum levels of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, matrix metalloproteinase (MMP)-1, and MMP-3 in patients with different stages of knee osteoarthritis (OA), and investigated the clinical significance of diagnosing OA in early stages. OA patients were divided into 2 groups: early OA group (44 cases), intermediate and advanced OA group (26 cases). The healthy control group included 30 samples. ADAMTS-4, ADAMTS-5, MMP-1, and MMP-3 levels in the serum were tested using an enzyme-linked immunosorbent assay. A protein-protein interaction network was constructed by seeding the significantly expressed marker, followed by Gene Ontology enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. ADAMTS-4 levels were significantly higher in patients at early stages of OA compared to intermediate or advanced OA and healthy controls. ADAMTS-5, MMP-1, and MMP-3 levels in intermediate and advanced-stage OA patients were significantly higher than those in early-stage OA patients and healthy controls. The protein-protein interaction network showed that ADAMTS-4 participates in 67 interactions. Gene Ontology enrichment analysis validated that genes associated with ADAMTS-4 participate in collagen metabolism and OA. ADAMTS-4 is a potential biomarker as an early diagnostic indicator of OA.

ADAMTS-1 and ADAMTS-4 levels are elevated in thoracic aortic aneurysms and dissections.

BACKGROUND: ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) is a recently identified family of extracellular metalloproteinases that has been shown to participate in tissue destruction. We hypothesized that ADAMTS-1 and ADAMTS-4 expression is increased in aortic tissues from patients with thoracic aortic aneurysms and dissections. METHODS: We examined ADAMTS-1 and ADAMTS-4 expression in human descending thoracic aortic aneurysms (n = 14), chronic descending thoracic aortic dissections (n = 16), and descending thoracic aortas from age-matched control organ donors (n = 12). In these tissues, we also evaluated the degradation of versican, a proteoglycan substrate of ADAMTS-1 and ADAMTS-4. In cultured macrophages, we examined whether ADAMTS-4 functions in macrophage infiltration by using a transwell assay. RESULTS: ADAMTS-1 and ADAMTS-4 protein and mRNA expression was significantly higher in thoracic aortic aneurysm and dissection tissues than in control aortic tissues. Double immunofluorescence staining showed the expression of ADAMTS-1 and ADAMTS-4 in smooth muscle cells and macrophages. Consistent with the upregulation of ADAMTS-1 and ADAMTS-4 in thoracic aortic aneurysm and dissection tissues, versican was degraded significantly more in these tissues than in control aortic tissues. In cultured macrophages, transforming growth factor-ß increased ADAMTS-4 protein levels and induced macrophage invasion, and the knockdown of ADAMTS-4 reduced cell invasion. CONCLUSIONS: Increased expression of ADAMTS proteins may promote thoracic aortic aneurysm progression by degrading versican and facilitating macrophage invasion.

Association of serum a disintegrin and metalloproteinase with thrombospodin motif 4 levels with the presence and severity of coronary artery disease.

OBJECTIVE: A disintegrin and metalloproteinase with thrombospodin motif 4 (ADAMTS4) has been shown to be an important player in atherosclerosis. However, the clinical significance of measuring serum ADAMTS4 levels has not been fully elucidated. We therefore investigate whether serum ADAMTS4 levels are associated with the presence and severity of coronary artery disease (CAD). METHODS: Serum levels of ADAMTS4 were measured in 192 patients undergoing elective coronary angiography for suspected CAD, the severity of CAD was determined by the number of diseased vessels and the severity score of coronary stenosis. RESULTS: Patients with CAD showed significantly higher levels of ADAMTS4 than did patients with normal coronary arteries [57.82 (48.96-70.32) vs. 46.55 (41.16-51.72) ng/ml, P<0.001]. ADAMTS4 levels increased with the number of diseased vessels (P<0.05) and significantly associated with severity score of stenosis (rs=0.601, P<0.001). In the multivariate analysis, ADAMTS4 levels were found to be independently correlated with the presence and severity of CAD. Receiver-operating characteristic analysis revealed that a cut-off of serum ADAMTS4 levels of 51.63 ng/ml could predict CAD with a 76% sensitivity and a 69% specificity. ADAMTS4 levels were significantly lower in patients with statin treatment than in those without it [47.49 (42.30, 57.09) vs. 56.39 (47.05, 68.94) ng/ml, P<0.05]. CONCLUSION: In conclusion, serum ADAMTS4 levels are associated with the presence and the severity of CAD, ADAMTS4 might serve as an independent factor for predicting CAD. Statin therapy reduces the serum levels of ADAMTS4.

ADAMTS4 level in patients with stable coronary artery disease and acute coronary syndromes.

OBJECTIVE: A recent study indicates that ADAMTS4 (a disintegrin and metalloprotease with thrombospondin motifs 4) was expressed in macrophage rich areas of human atherosclerotic carotid plaques and coronary unstable plaques suggesting a pathogenic role in the development of acute coronary syndromes (ACS). The aim of the study was to compare ADAMTS4 across the entire spectrum of coronary artery disease (CAD) and to investigate the temporal profiles of ADAMTS4. METHODS: Plasma levels of ADAMTS4 were measured in patients with stable effort angina pectoris (SAP), ACS and in controls. Venous blood was sampled upon admission before angiography and drug administration. In patients with ACS who underwent medical treatment, serial blood samples were also collected on days 1, 2, 3, 5 and 7 after admission. ADAMTS4 was measured using an enzyme immunoassay. RESULTS: Plasma ADAMTS4 level in cases was significantly greater than in controls (P<0.001). Higher levels of ADAMTS4 were found with progression of CAD from SAP to unstable angina pectoris (UAP) to non-ST-segment elevation acute myocardial infarction (NSTEMI) and to ST-segment elevation acute myocardial infarction (STEMI) (P<0.001). Elevated ADAMTS4 level was associated with ACS with an area under receiver operating characteristic (ROC) curve of 0.753 (95% CI 0.654-0.851; P<0.001). The pattern of ADAMTS4 release observed was clearly different in various forms of ACS. ADAMTS4 showed a weak correlation with high-sensitivity C-reactive protein (hs-CRP); however, no significant correlation was found between ADAMTS4 and troponin T (TnT) in ACS patients. CONCLUSIONS: Serial changes in plasma ADAMTS4 were documented in patients with ACS and may serve as a marker of plaque destabilization.

Time course of osteocalcin, bone-specific alkaline phosphatase, and C-terminal procollagen peptide during callus distraction.

This study involved 15 patients who were undergoing extremity lengthening by callus distraction. Blood samples and radiographs of the callus distraction segment were obtained before surgery, every 2 weeks during the distraction phase, and every 4 weeks between the end of distraction and removal of the fixator. A digital radiograph analysis system was used to determine the radiographic density of the callus distraction segments. In addition, the serum parameters osteocalcin, bone-specific alkaline phosphatase, and C-terminal procollagen peptide (PICP) were evaluated. The radiographic density was constant during the distraction phase, but increased logarithmically during the consolidation period. Similar kinetics were observed for osteocalcin, with an average coefficient of correlation between these two parameters of 0.66+/-0.15. PICP levels rose rapidly after surgery and increased further during the consolidation period. Serum levels of bone-specific alkaline phosphatase were not uniform between patients, and there was no correlation to the kinetics of radiographic density or the other serum parameters. The similarity between radiographic density and osteocalcin kinetics, as well as the rapid postoperative increase in PICP, imply that further information may be obtained about osteoneogenesis from the study of these two serum parameters.

Serum peptide III-procollagen and ACE in asbestos workers.

Type-III-procollagen peptide (P-III-P) concentration and angiotensin-converting-enzyme (ACE) activity were measured in the serum of asbestos workers. The subjects were classified into four groups (A, B, C, D) according to the duration of exposure (in years). A gradual increase of ACE activity in group B and P-III-P concentration in group C was found. The increase in ACE activity can be regarded as the response to the progressing inflammatory state, and the increase in P-III-P concentration may be related to the fibrosis of the lung tissue.

Serum type III procollagen peptides in patients with hepatointestinal and compensated hepatoesplenic schistosomiasis forms

Os níveis dos peptídios séricos do procolágeno tipo III (PSPC III) foram determinados em 35 indivíduos: 25 esquistossomóticos näo tratados da parasitose, sendo 16 da forma hepatointestinal (HI) e nove da hepatoesplênica compensada (HEC) e dez sadios. Para a dosagem dos PSPC III foram utilizados kits de radioimunoensaio. Procurou-se demonstrar a correlaçäo entre os níveis dos PSPC III e as atividades séricas das enzimas aminotransferase da alanina (ALT), aminotransferase do aspartato (AST), fosfatase alcalina (FA) e gamaglutamiltranspeptidase (GGTP). As médias dos valores dos PSPC III nas formas HI (13 ng/ml) e HEC (17 ng/ml) foram significantemente maiores do que as do grupo controle (9,0 ng/ml) (p < 0,05). Näo se observou diferença significante quanto aos valores dos PSPC III entre os grupos de pacientes das formas HI e HEC. Näo houve correlaçäo entre os aumentos dos PSPC III e os da atividade sérica da ALT, AST, FA e GGPT. Os autores discutem aspectos sobre eventual aplicabilidade da determinaçäo dos PSPC III em pacientes com esquistossomose