Serum Levels Of Metalloproteinase Research Articles

The Effect of Calcineurin Inhibitors on MMPs Activity in Heart and Their Side Effects-A Review of Literature.

This review focuses on the role of metalloproteinases in the pathogenesis of myocardial injury in various disease entities. It reveals how the expression and serum levels of metalloproteinases and their inhibitors change in many disease states. At the same time, the study offers a review of the impact of immunosuppressive treatment on this relationship. Modern immunosuppressive treatment is based mainly on the use of calcineurin inhibitors, including cyclosporine A and tacrolimus. The use of these drugs may carry a number of side effects, specifically to the cardiovascular system. The scale and degree of long-term influence on the organism remains unclear, but a significant risk of complications for transplant recipients who take immunosuppressive drugs as part of their daily treatment is to be expected. Therefore, the knowledge on this subject should be expanded and the negative effects of post-transplant therapy minimized. Immunosuppressive therapy plays an important role in the expression and activation of tissue metalloproteinases and their specific inhibitors, which leads to many tissue changes. The presented study is a collection of research results on the effects of calcineurin inhibitors on the heart, with particular emphasis placed on the participation of MMP-2 and MMP-9. It is also an analysis of the effects of specific heart diseases on myocardial remodeling through inductive or inhibitory effects on matrix metalloproteinases and their inhibitors.

Sensitive methods for assessment of lung health in welders and controls

BackgroundWelders are exposed to gas and particle emissions that can cause severe lung disease, such as chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity worldwide. It is difficult to detect COPD early and therefore mitigating measures may be delayed. The aim of this study was to investigate lung health in welders and evaluate new sensitive methods with potential to assess early onset pulmonary changes in occupational settings. MethodsThis study assessed the lung health and symptoms in active welders (n = 28) and controls (n = 17). Lung measurements were performed with standard spirometry and new methods: airspace dimension assessment (AiDA), oscillometry, blood serum biomarkers (club cell secretory protein 16, surfactant protein D, matrix metalloproteinases, fibroblast, hepatocyte growth factor, interleukins), and one urine biomarker (desmosine). ResultsAccording to spirometry measurements, all participants had normal lung function. However, prevalence of cough was significantly higher among welders compared with controls and lung changes were found in welders with the novel methods. Welders had significantly higher respiratory system resistance assessed with oscillometry, serum levels of metalloproteinases 9 and hepatocyte growth factor, compared with controls. Airspace dimensions were on average higher among welders compared with controls, but the difference was not significant. The number of welding years correlated with decreased respiratory system reactance and increased serum levels of matrix metalloproteinases 9, interleukin 6, and hepatocyte growth factor. Airspace dimension assessment indices were correlated with increasing levels of inflammatory markers and matrix metalloproteinases. ConclusionsThis study indicated the potential to use new and more sensitive methods for identification of changes in lungs when standard spirometry failed to do so.

Association of Matrix Metalloproteinases with Coronary Artery Calcification in Patients with CHD

This work is aimed at studying the relationship of matrix metalloproteinases with calcification of the coronary arteries. The study included 78 people with coronary heart disease (CHD) and 36 without CHD. Blood and samples of coronary arteries obtained as a result of endarterectomy were examined. Serum levels of metalloproteinases (MMP) MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13 were determined by multiplex analysis. In blood vessel samples, MMP-1, MMP-3, MMP-7, and MMP-9 were determined by enzyme immunoassay; MMP-9 expression was evaluated by immunohistochemistry. Patients with CHD had higher serum levels of MMP-1, MMP-7, and MMP-12. Blood levels of MMP-1 and MMP-3 were associated with calcium levels, MMP-9 with osteoprotegerin and osteonectin, MMP-7 and MMP-10 with osteoprotegerin, MMP-12 with osteocalcin, and MMP-13 with osteopontin. Calcified plaques had higher levels of MMP-1 and MMP-9 compared to plaques without calcification. The relative risk of coronary arteries calcification was associated with MMP-9, which is confirmed by the results of immunohistochemistry. The results obtained indicate the participation of some MMPs, and especially MMP-9, in the calcification processes. The study can serve as a basis for the further study of the possibility of using MMP-1, MMP-7 and MMP-12 as potential biomarkers of CHD.

Metabolites of type I, II, III, and IV collagen may serve as markers of disease activity in axial spondyloarthritis

Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A total of 193 axSpA patients (nr-axSpA, n = 121 and AS, n = 72) and asymptomatic controls (n = 100) were included. Serum levels of metalloproteinase (MMP)-degraded collagen type I (C1M), type II (C2M), type III (C3M) and type IV (C4M2) were quantified by enzyme-linked immunosorbent assay (ELISA). All metabolites were higher in axSpA than in controls (all p < 0.001). Serum levels of C1M, C3M, and C4M2 were increased in AS compared to nr-axSpA (43.4 ng/mL vs. 34.6; p < 0.001, 15.4 vs. 12.8; p = 0.001, and 27.8 vs. 22.4; p < 0.001). The best metabolite to differentiate between axSpA and controls was C3M (AUC 0.95; specificity 92.0, sensitivity 83.4). C1M correlated with ASDAS-CRP in nr-axSpA (ρ = 0.37; p < 0.001) and AS (ρ = 0.57; p < 0.001). C1M, C3M, and C4M2 were associated with ASDAS-CRP in AS and nr-axSpA after adjustment for age, gender, and disease duration. Serum levels of collagen metabolites were significantly higher in AS and nr-axSpA than in controls. Moreover, the present study indicates that collagen metabolites reflect disease activity and are useful biomarkers of axSpA.

New Drug Avenues for Cardioprotection in Patients with Acute Myocardial Infarction

Acute myocardial infarction (AMI) is a leading cause of heart failure and premature death worldwide [1]. Both immediate medical treatment and rapid reperfusion to limit myocardial damage are strongly recommended [2, 3]. However, reperfusion has the potential to initiate additional lethal injury, known as ‘ischemia–reperfusion (IR) injury,’ and could result in increased cardiac cell death [4]. New therapeutic strategies that directly target the reperfusionmediated damage have been proved to reduce infarct size (IS) in experimental animal models. These approaches include (1) ischemic postconditioning [5, 6] and even remote postconditioning [7]; (2) pharmacological postconditioning including cyclosporine A [8] or normalization of intracellular calcium homeostasis [9, 10]; and (3) genetic perturbation in animal models of critical proapoptotic pathways involved in reperfusion injury [11, 12]. These new approaches have been shown to improve ventricular remodeling and clinical outcomes after AMI [13–17]. IR lesions are partly mediated and worsened by oxidative stress [18]. One of the most known anti-oxidative agents is N-acetylcysteine (NAC), but results in clinical translation have been most often disappointing as regards cardiovascular disease [19] as well as nephrology [20]. Nevertheless, NAC is currently under study in various fields of medical research, as briefly presented in the Table 1, noticeably in psychiatry disorders. This venerable drug had been already proposed as an interesting candidate for cardioprotection for decades [21–24], but controversial results have been obtained. In this issue of the Journal, Talasaz et al. [25] once again address the efficacy of NAC to control post-MI remodeling. They suggest that NAC could improve the myocardial remodeling following AMI in a proof-ofconcept clinical trial. In this prospective, double-blinded, randomized clinical trial, 98 patients were allocated to placebo or NAC at the dose of 600 mg orally twice daily during three days upon hospital arrival. The authors showed that serum levels of metalloproteinase (MMP)-9 and MMP-2 after 72 h and major adverse cardiac events including re-infarction during the 1-year follow-up were significantly lower in the treated group than in the placebo group. However, several limitations have to be underlined, and this proof-of-concept trial has to be confirmed in larger trials. Among the limitations, mainly biochemical and baseline echographic parameters have been considered, so it is difficult to conclude on echocardiographic evolution, IS (whether this was accurately measured) or specific clinical outcomes. Reperfusion is not always obtained (only 40 % of the patients received primary coronary intervention), collateral flow or area at risk are not taken into consideration, and, importantly, the sample is small. Whether the design of the study, especially the timing (as soon as possible to treat the IR lesions), the route (would intravenous/intracoronary route, if safe, be more efficient?), and the very drug under study, including This paper is a commentary on the original paper at doi:10.1007/s40256-013-0048-x.

AB0111 Extracellular 14-3-3 ETA represents a novel rheumatology biomarker and drug target for personalized medicine

Background14-3-3η is a novel therapeutic target that stimulates specific cell lines (THP-1), activates disease-specific pathways (MAPK) and potentiates pathogenic factors (TNFα, IL-6). Clinically, 14-3-3η serum expression is higher in both...

Serum levels of metalloproteinases and their inhibitors during infection with pathogens having integrin receptor-mediated cellular entry

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with numerous roles in the normal immune response to infection. However, excess MMP activity following infection may lead to immunopathological processes that cause tissue damage. Their activity in normal tissues is subject to tight control, which is regulated by its specific endogenous tissue inhibitors (TIMPs). It is known that MMPs bind to cell surface proteins (e.g. integrins) and that such interactions can have modulatory effects on MMP functionality. The objective of this study was to determine whether there are differences in MMP and TIMP production during the acute phase of infection with different pathogens that use β-integrins as their receptors for cell entry. We measured the total amounts of soluble MMP-2, MMP-9, TIMP-1, and TIMP-2 in the sera from patients infected with Dobrava virus (DOBV), Coxiella burnetii, or uropathogenic Escherichia coli. Statistical analyses were used to correlate MMP/TIMP serum levels with different clinical laboratory parameters. The results showed that both of the bacterial infections generally manifested the stronger effect on MMP production, while in contrast, viral infection introduced stronger changes to metalloproteinase inhibitors. MMPs and TIMPs were significantly correlated with some of the clinical laboratory parameters in both bacterial infections, but no correlations were found for DOBV infection. These findings suggest diverse mechanisms by which MMP activity could be implicated in the pathology of these 2 bacterial infections versus the viral DOBV infection, despite the type of their cellular entry receptors.

Noninvasive Diagnosis of Hepatic Fibrosis in HIV/HCV-Coinfected Patients

Several serum markers reflecting extracellular matrix status have been correlated with liver fibrosis in non-HIV-infected patients with chronic hepatitis C infection. These indexes have been less examined in HIV/HCV-coinfected individuals. We aimed to evaluate the predictive value of serum markers for liver fibrosis in HIV-infected patients with chronic hepatitis C virus (HVC). Serum levels of metalloproteinases 1 and 2 (MMP-1 and -2), tissue inhibitors of matrix metalloproteinases (TIMP-1), procollagen type III N-terminal peptide (PIIINP), and hyaluronic acid (HA) were measured in HIV-infected patients with chronic hepatitis C at the time of obtaining a liver biopsy and before the consideration of anti-hepatitis C therapy. One hundred and nineteen consecutive HIV-HVC coinfected patients were included. TIMP-1 (r = 0.6; P < 0.001), TIMP-1/MMP-1 ratio (r = 0.5; P < 0.001), TIMP-1/MMP-2 ratio (r = 0.3; P < 0.001), MMP-2 (r = 0.2; P = 0.044), PIIINP (r = 0.4; P < 0.001), and HA (r = 0.5; P < 0.001) were positively and significantly correlated with the fibrosis stage. In the multivariate analysis, TIMP-1 (odds ratio [OR] = 1.004, 95% confidence interval [CI]: 1.002 to 1.006, P = 0.001) and HA >95 microg/dL (OR = 6.041, 95% CI: 1.184 to 30.816, P = 0.031) were independently associated with liver fibrosis. The area under the curve of score to discriminate mild (F0-F1) from significant (F2-F4) fibrosis in the received-operating analysis using the variables TIMP-1 and HA was 0.84, with a sensitivity of 72.9% and a specificity of 83.1%. TIMP-1 and HA were quite sensitive and specific for predicting the degree of liver fibrosis in HIV-infected patients with chronic hepatitis C. These parameters may become a noninvasive alternative to liver biopsy when the degree of liver fibrosis needs to be estimated.

Heterogeneity of serum activities of matrix metalloproteinases in chronic endometritis

Matrix metalloproteinases belong to the key molecules of tissue remodeling involved in physiological and pathological processes of the female reproductive system. Adequate levels of their expression in the endometrium are essential for effective implantation and uneventful pregnancy. Chronic inflammatory process in the endometrium is associated with low tissue expression of metalloproteinase-9. Histologically verified chronic endometritis is associated with low serum activities of metalloproteinases 2 and 9, which are restored after combined etiotropic therapy. We measured serum levels of metalloproteinases in patients with chronic endometritis concomitant with sterility and its changes during the first days after magnetotherapy.

Changes in serum levels of metalloproteinases and their inhibitors by treatment of chronic hepatitis C with interferon

We treated 18 patients with chronic hepatitis C by recombinant interferon-alpha (6 MIU for 24 weeks). In seven patients, serum aminotransferase levels declined to normal (responders). To evaluate the effect of interferon on matrix metalloproteinases (MMPs) and their inhibitors, namely tissue inhibitors of metalloproteinases (TIMPs), the serum levels of these enzymes were determined by enzyme immunoassay (EIA) using a specific monoclonal antibody. In responders, there was a tendency, but not a significant one, towards either an increase in serum MMP 1 levels or a decrease in serum TIMP 1 levels. In contrast, in nonresponders, both a significant decrease in MMP 1 and MMP 3 and a significant increase in TIMP 1 were observed. The number of cases of either increase in serum MMP levels or decreased in serum TIMP levels was significantly larger in responders than in nonresponders. Furthermore, the ratio of MMP 1 to TIMP 1 significantly increased in responders, suggesting that the balance between matrix formation and degradation in hepatic fibrosis tended to move toward degradation. These data indicate that interferon may exert a beneficial effect on hepatic fibrosis in parallel with improvement of aminotransferase activity.