Features of the level of matrix metalloproteinase-2, -3, -9 and tissue inhibitors of metalloproteinases-1, -2, -3, -4 in the aqueous humor of patients with primary open-angle glaucoma

Aim. To study the content of matrix metalloproteinase (MMP)-2, -3, -9 and tissue inhibitors of metalloproteinases (TIMPs) -1, -2, -3, -4 in the aqueous humor of patients with moderate primary open-angle glaucoma (POAG).Materials and methods. The experimental group included 47 patients with verified moderate primary open-angle glaucoma. The control group consisted of 26 patients with uncomplicated cataract. The levels of MMP-2, -3, -9 were determined with Luminex Performance Human MMP Magnetic Panel 3-plex kit (R&D Systems, USA), the concentration of TIMPs-1, -2, -3, - 4 was determined with the Human TIMP Magnetic Luminex Performance Assay 4-plex kit (R&D Systems, USA). The study was carried out using flow-through field fluorometry on a Bio-Plex 200 double-beam laser analyzer (Bio-Rad, USA).Results. The study showed a statistically significant increase in the levels of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinases-1, -2, -3, -4 in the aqueous humor of patients with moderate POAG compared with patients with uncomplicated cataract.Conclusion. The obtained data on high concentrations and imbalance in the levels of matrix metalloproteinases and their tissue inhibitors in the aqueous humor of patients with moderate POAG confirm the role of local inflammation, as well as impairments in the structure of the extracellular matrix and its remodeling in the mechanisms of development of this pathology.

Activity of genes of matrix metalloproteinases and their inhibitors in the Ligamentum flavum of patients with stenosing processes in spinal canal and dural sac

New data have been obtained for assessing the expression of genes of metalloproteinases and their tissue inhibitors (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1 and TIMP-2) in the Ligamentum flavum in patients with lumbar stenosis of spinal canal and dural sac. The features of the metabolism of the extracellular matrix (ECM) were revealed, the data obtained were compared with those for previously studied candidate genes. The search for relationships with the features of the ECM metabolic characteristics was carried out.The aim. To study the expression of genes of metalloproteinases and their tissue inhibitors in intraoperative biopsies of the Ligamentum flavum of patients with lumbar stenosis of the spinal canal and dural sac.Materials and methods. A group of 33 people (17 women, 16 men) with lumbar stenosis of the spinal canal and dural sac was studied; the average age is 45.73 ± 1.95 years. RNA was isolated from intraoperative biopsies of the Ligamentum flavum, reverse transcription was performed, and PCR using specific primers was performed.Results. In Ligamentum flavum of patients with stenosing processes of the spinal canal and dural sac, an increased activity of MMP-1 and insufficient response of TIMP-1 and TIMP-2 were found; the expression of MMP-1 increased synchronously with Dio2, and both genes decreased their activity with increasing age of the patient. In patients with Ligamentum flavum ossification, the MMR-8 gene was more actively expressed, and the synthesis of the mRNA of the MMR-9 gene decreased compared to the subgroup without ossification.

EFFECT OF THE ANTIVIRAL DRUG KAGOCEL® ON THE LEVELS OF MATRIX METALLOPROTEINASES MMP-8 AND MMP-9 AND THEIR TISSUE INHIBITORS TIMP-1 AND TIMP-2 IN INDUCED SPUTUM IN THE COMBINED TREATMENT OF COMMUNITY-ACQUIRED VIRAL-BACTERIAL PNEUMONIA

The effect of the antiviral drug Kagocel on the levels of metalloproteinases MMP-8 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in induced sputum in the treatment of community-acquired viral-bacterial pneumonia was analyzed. 60 adult patients with a confirmed diagnosis of community-acquired pneumonia and viral-bacterial etiology were included in the follow-up research work. Materials and methods. All patients were randomly divided into 2 groups: 1 group (comparison group) included 30 patients receiving Ceftriaxone monotherapy; in the 2nd group (main) - 30 people who were prescribed Ceftriaxone and the antiviral drug Kagocel as etiotropic treatment. Both groups were comparable in terms of gender, age and time of admission to the hospital. Results. During hospitalization, patients in both groups had elevated levels of MMP-8, MMP-9, TIMP-1 and TIMP-2 in induced sputum compared to the reference values. By 7 days of inpatient treatment, the level of MMP-8 continued to be significantly higher than the reference values ​​in both groups, and in patients of the 2nd group there was a decrease compared to baseline values, and in patients in the 1st group at the same time. The activity of MMP-9 during hospitalization was also high in patients of both groups compared with the level of these enzymes in healthy people. By the 7th day of therapy various indicators' changes were recorded. The level of MMP-9 in patients of the 1st group increased, and in patients of the 2nd group - on the contrary - decreased. The level of TIMP-1 decreased in patients of the 1st group below the control value, and in patients of the 2nd group - reached the reference values. The level of TIMP-2 decreased in both groups and reached the level of control values. Conclusion. Inclusion in the standard antibacterial regimen of community-acquired viral-bacterial pneumonia of the antiviral drug Kagocel reduces the level of MMR-9 and reduces the severity of the imbalance in the MMP and TIMP system by 7 days of therapy, which leads to a faster clinical recovery of patients.

A Review on the Relationship between Matrix Metalloproteinases (Mmps) and their Natural Inhibitors (Tissue Inhibitors Of Matrix Metalloproteinases [Timps]) and the Success of an Autologous Arteriovenous Fistula (Avf)

Since its introduction by Brescia and Cimino in 1966, arteriovenous fistula has been regarded as the best vascular access for haemodialysis purpose. However, it’s not without any drawbacks which has cost over USD1 billion in the United States alone to rectify them. Intimal hyperplasia has been shown to be a major contributory factor to this development. Intimal hyperplasia is a complex molecular process resulting in unwarranted accumulation of contractile smooth muscle cells, myofibroblasts, fibroblasts, and macrophages. There is an increasing amount of evidence suggesting that matrix metalloproteinases (MMPs) and its natural inhibitors (tissue inhibitors of matrix metalloproteinases ([TIMPs]) play a pivotal role in the development of intimal hyperplasia. Our purpose of writing this review article is to examine these evidences and to suggest of what future research questions need to be answered to further strengthen and clarify this relationship.

Association of Polymorphisms of the Tissue Inhibitors of Metalloproteinases-1 and -2 with Alzheimer’s Disease in Taiwan

Background: Alzheimer’s disease (AD) leads to progressive neuronal loss and cognitive and behavioral decline in the aging population. Matrix metalloproteinases (MMPs) and associated tissue inhibitors of metalloproteinases (TIMPs) are involved in remodeling the extracellular matrix. Amyloid beta-42 interrupts the integrity of the neurovascular unit and induces a toxic reaction affecting neurons. Objective: This study investigated the relationships among genetic variants of the MMP-2, MMP-9, TIMP-1, and TIMP-2 genes and AD. Methods: Two hundred and thirteen probable AD patients and 315 control participants of the Tai- wan population were recruited for primary investigations, and we used the data of 763 participants from the Taiwan Biobank (TWB), as controls, for validation. Multivariable logistic regression was performed with adjustments for age, sex, hypertension, diabetes mellitus (DM), and alcohol con- sumption. The associations between the genotypes and allele frequencies and the SNP-associated AD hereditary models were analyzed using the SNPassoc package for R. We performed a permuta- tion test with 1,000 replicates for the empirical estimates. Results: A total of 213 probable AD patients and 315 control participants were recruited. The fre- quency of the A alleles in rs7503726 (G > A) in TIMP-2 was lower in the AD patients (p < 0.01). The frequencies of the TIMP-2 rs7503726 G/A and A/A genotypes were also significantly lower in the AD patients (p = 0.02) than in the controls and TWB. The TIMP-2 rs7503726 AA genotype was associated with a protective effect of AD in additive and recessive hereditary models (OR = 0.54, 95% CI: 0.32 – 0.92, p = 0.02; OR = 0.68, 95% CI: 0.50 – 0.92, p = 0.01, respectively). Conclusion: The TIMP-2 rs7503726 AA genotype was inversely correlated with AD susceptibili- ty, and the presence of minor alleles of rs7503726 (A allele) have protective effects against AD.

Expression of tissue inhibitors of metalloproteinases type 1 and type 2 in the leaflets of explanted bioprosthetic heart valves: a new pathogenetic parallel between structural valve degeneration and calcific aortic stenosis

Objective: to study cellular and lipid infiltration, as well as the expression of tissue inhibitors of metalloproteinases (TIMP) types 1 and 2 in biological prosthetic heart valves (BPHVs) explanted due to dysfunction.Material and Methods. We examined 17 leaflets from 6 BPHVs, dissected from the aortic and mitral positions during valve replacement. For microscopic analysis, fragments of the BPHV leaflets were frozen and serial sections were made using a cryotome. In order to study cellular infiltration and the degree of degenerative changes in the prosthetic biomaterial, the sections were stained with Gill’s hematoxylin and eosin; Oil Red O stain was used to assess lipid deposition. Immunohistochemistry was used for cell typing and detection of TIMP-1/-2. The stained samples were analyzed by light microscopy.Results. Cellular and lipid infiltration of xenogeneic tissues was detected in all BPHV flaps studied. Recipient cells coexpressed pan-leukocyte and macrophage markers PTPRC/CD45 and CD68. Positive staining for TIMP-1/-2 co-localized with cell clusters but was absent in acellular sections.Conclusion. Cells infiltrating xenogeneic BPHV tissues express TIMP-1/-2. This suggests that BPHV immune rejection pathophysiology is partially similar to that of calcific aortic stenosis.

Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Echinoderms: Structure and Possible Functions

Echinoderms are one of the most ancient groups of invertebrates. The study of their genomes has made it possible to conclude that these animals have a wide variety of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The phylogenetic analysis shows that the MMPs and TIMPs underwent repeated duplication and active divergence after the separation of Ambulacraria (Echinodermata+Hemichordata) from the Chordata. In this regard the homology of the proteinases and their inhibitors between these groups of animals cannot be established. However, the MMPs of echinoderms and vertebrates have a similar domain structure. Echinoderm proteinases can be structurally divided into three groups—archetypal MMPs, matrilysins, and furin-activatable MMPs. Gelatinases homologous to those of vertebrates were not found in genomes of studied species and are probably absent in echinoderms. The MMPs of echinoderms possess lytic activity toward collagen type I and gelatin and play an important role in the mechanisms of development, asexual reproduction and regeneration. Echinoderms have a large number of genes encoding TIMPs and TIMP-like proteins. TIMPs of these animals, with a few exceptions, have a structure typical for this class of proteins. They contain an NTR domain and 10–12 conservatively located cysteine residues. Repeated duplication and divergence of TIMP genes of echinoderms was probably associated with an increase in the functional importance of the proteins encoded by them in the physiology of the animals.

Modulation of the Extracellular Signal-Regulated Protein Kinase and Tissue Inhibitors of Matrix Metalloproteases-1 Gene in Chronic Neuropathic Pain

Objectives: The aim of this study is to study the modulation of extracellular signal-regulated protein kinase (ERK) and tissue inhibitors of matrix metalloproteases 1 (TIMP 1) gene in patients with neuropathic pain (NP). Materials and Methods: In the present, cross-sectional, observational study, 2 ml of venous baseline sample was withdrawn from all the patients with neuropathic (NP) or non NP (NNP) soon after their diagnosis or on their first visit to the pain clinic. A real-time quantitative polymerase chain reaction experiment was conducted to measure the mRNA expression of TIMP1 and ERK genes in blood samples. The Delta Ct, Delta Ct, and fold change analysis of both the genes were conducted between patients with NP and NNP. Results: A total of 285 patients with chronic pain were assessed, out of which, 153 patients had NP and 132 had NNP. The average duration of chronic pain was 11 months for 285 patients. The mRNA expression of TIMP1 gene is significantly down regulated (2.65-fold) (P (-f. 01), and the mRNA expression level of ERK is significantly up regulated (2.03-fold) (P (-f. 01) in NP patients when compared with NNP. Conclusion: The mRNA expression of TIMP1 gene is significantly down regulated, and ERK is significantly up regulated in patients with NP. Further, multicentric trials with larger sample size are recommended to confirm this finding.