Matrix metalloproteinases (MMPs), endopeptidases degrading extracellular matrix, play an important role in the pathogenesis of atherosclerosis and vascular disease. The aim of this study was to evaluate the association between the C(-1562)T functional polymorphism in the MMP-9 gene and risk of stroke. We examined 322 patients with stroke and 410 controls. In the patient group, 52 % had type 2 diabetes. All subjects were genotyped for the C(-1562)T polymorphism by polymerase chain reaction and restriction analysis. A significant increase in T allele and CT + TT genotype frequencies was observed in patients compared with controls (OR 1.73, 95 % CI 1.34-2.23 and 1.89, 95 % CI 1.39-2.56, respectively). The T allele carriers were younger at the onset of stroke (63.5 ± 11.7 years) than patients with CC genotype (71 ± 14.1 years) (p = 0.0002). The comparison between patients with T2DM and without it showed that the T allele and CT + TT genotype were more frequent in T2DM patients (OR 1.48, 95 % CI 1.03-2.12 for T allele and 1.44, 95 % CI 1.93-2.24 for CT + TT genotype). In conclusion, our findings suggest that MMP-9 C(-1562)T polymorphism is significantly associated with risk of stroke in patients with and without T2DM.

Matrix metalloproteinase (MMP) is involved in the upper airway remodeling process. We hypothesized that genetic variants of the MMP-9 gene are associated with cases of chronic rhinosinusitis with nasal polyposis.

The role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in sepsis after major abdominal surgery and sepsis-associated organ dysfunction is unexplored.

Temporal lobe epilepsy (TLE) is a devastating disease in which aberrant synaptic plasticity plays a major role. We identify matrix metalloproteinase (MMP) 9 as a novel synaptic enzyme and a key pathogenic factor in two animal models of TLE: kainate-evoked epilepsy and pentylenetetrazole (PTZ) kindling-induced epilepsy. Notably, we show that the sensitivity to PTZ epileptogenesis is decreased in MMP-9 knockout mice but is increased in a novel line of transgenic rats overexpressing MMP-9. Immunoelectron microscopy reveals that MMP-9 associates with hippocampal dendritic spines bearing asymmetrical (excitatory) synapses, where both the MMP-9 protein levels and enzymatic activity become strongly increased upon seizures. Further, we find that MMP-9 deficiency diminishes seizure-evoked pruning of dendritic spines and decreases aberrant synaptogenesis after mossy fiber sprouting. The latter observation provides a possible mechanistic basis for the effect of MMP-9 on epileptogenesis. Our work suggests that a synaptic pool of MMP-9 is critical for the sequence of events that underlie the development of seizures in animal models of TLE.

Acute coronary syndrome (ACS) is characterized by increased inflammatory processes and endothelial activation. We investigated the association between ACS and inflammatory mediators and matrix-degrading enzymes.

Extracranial arteriovenous malformations (AVMs) are rare but dangerous congenital lesions arising from direct arterial-venous shunts without intervening capillaries. Progressive infiltration, expansion, and soft tissue destruction lead to bleeding, pain, debilitation and disfigurement. The pathophysiology of AVMs is not well understood. Matrix Metalloproteinases (MMPs) are thought to play an important role in pathologic processes underlying many diseases. This study investigates the expression of MMP-9 and MMP-2 in aggressive extracranial AVMs. The differential expression of MMP-9 and its regulatory factors is also examined. Herein we demonstrate that mRNA and protein expressions of MMP-9, but not MMP-2, are significantly higher in AVM tissues compared to normal tissues. The serum level of MMP-9, but not MMP-2, is also elevated in AVM patients compared to healthy controls. MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex is also significantly increased in AVM tissues. The MMP-9/ tissue inhibitor of metalloproteases-1 (TIMP-1) complex presents as a major form detected in normal tissues. The increased and aberrant expression of MMP-9 and specific MMP-9 forms may help explain the constitutive vascular remodeling and infiltrative nature of these lesions. Specific MMP-9 inhibitors would be a promising treatment for AVMs.

Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs) play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk.

Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability.

Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of cancer, autoimmune disease, and various pathologic conditions characterized by excessive fibrosis. In this study, we investigated the expression of MMP-9 and its clinical significance in systemic sclerosis (SSc). The patients (n = 42) with SSc had higher concentrations of MMP-9 and of tissue inhibitor of metalloproteinase-1 (TIMP-1) and a higher ratio of MMP-9 to TIMP-1 in sera than healthy controls (n = 32). Serum MMP-9 concentrations were significantly higher in the diffuse type (n = 23) than the limited type of SSc (n = 19). Serum concentrations of MMP-9 correlated well with the degree of skin involvement, as determined by the Rodnan score and with serum concentrations of transforming growth factor beta. Moreover, dermal fibroblasts from patients with SSc produced more MMP-9 than those from healthy controls when they were stimulated with IL-1beta, tumor necrosis factor alpha, or transforming growth factor beta. Such an increase in MMP-9 production was partially blocked by treatment with cyclosporin A. In summary, the serum MMP-9 concentrations were elevated in SSc patients and correlated well with skin scores. The increased MMP-9 concentrations may be attributable to overproduction by dermal fibroblasts in SSc. These findings suggest that the enhanced production of MMP-9 may contribute to fibrogenic remodeling during the progression of skin sclerosis in SSc.

The phenomenon of dendritic transport and local translation of mRNA is considered to be one of the most fundamental mechanisms underlying long-term synaptic plasticity. Matrix metalloproteinase 9 (gelatinase B) (MMP-9) is a matrix metalloproteinase implicated in synaptic long-term potentiation and hippocampus-dependent memory. It was recently shown to be prominently up-regulated in the hippocampal dentate gyrus (DG) upon kainate-mediated seizures. Here, using a high resolution nonradioactive in situ hybridization at the light- and electron-microscopic levels, as well as subcellular fractionation, we provide evidence that in the rat hippocampus, MMP-9 mRNA is associated with dendrites and dendritic spines bearing asymmetric (excitatory) synapses. Moreover we observe that after kainate treatment the number of dendrites and synapses containing MMP-9 mRNA increases markedly. Our results indicate that we are observing the phenomenon of dendritic transport of seizure-induced MMP-9 mRNA.

Previous studies have found that some ventricular remodeling is accompanied by increased matrix metalloproteinase-9 (MMP-9) in vivo, and MMP-9 inhibitors can reduce ventricular remodeling. However, there is still no direct evidence that MMP-9 causes ventricular remodeling. In this study, MMP-9 was injected into rats to observe whether MMP-9 caused ventricular remodeling, thereby providing direct evidence of MMP-9-induced ventricular remodeling.

Matrix metalloproteinase 9 (MMP-9) plays an important role in inflammatory and pathological processes by enabling the inflow of leukocytes to the site of infection or tissue damage. MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) have been described as potential prognostic biomarkers in various clinical settings. The aim of the study was to evaluate the usefulness of plasma levels of MMP-9 and TIMP-1 as well as the MMP-9/ TIMP-1 ratio in predicting the outcome in patients admitted to the intensive care unit (ICU). The study included 56 critically ill patients with multiple organ failure. Plasma levels of MMP-9 and TIMP-1 were determined on hospitalization day 1, 2, 3 and 7. Nineteen (35.7%) patients died. The level of TIMP-1 was statistically significantly higher on day 1 and 7 of hospitalization in non-survivors, as compared to survivors (p=0.01). A statistically significant positive correlation was found between MMP-9 and TIMP-1. The MMP-9/TIMP-1 ratio was comparable in both groups during of observation (0.62 on day 1). The MMP-9/TIMP-1 ratio was positively correlated with the level of lactate and negatively correlated with platelet count. Likewise, TIMP-1 was positively correlated with the level of lactate. The level of MMP-9 was higher in the non-survivor group only on day 7 of observation. In conclusion, although TIMP-1 and MMP-9 concentrations were higher in non-survivors and the MMP-9/TIMP-1 ratio was related to some parameters of critical illness, further research is needed to verify whether they can serve as reliable biomarkers for early prognostication of ICU patients.

Deep venous thrombosis is a common vascular problem with long-term complications including post-thrombotic syndrome. Post-thrombotic syndrome consists of leg pain, swelling and ulceration that is related to incomplete or maladaptive resolution of the venous thrombus as well as loss of compliance of the vein wall. We examine the role of metalloproteinase-9 (MMP-9), a gene important in extracellular remodeling in other vascular diseases, in mediating thrombus resolution and biomechanical changes of the vein wall.

Brain injury activates complex inflammatory signals in dying neurons, surviving neurons, and glia. Here, we establish that inflammation regulates the regeneration of photoreceptors in the zebrafish retina and determine the cellular expression and function of the inflammatory protease, matrix metalloproteinase 9 (Mmp-9), during this regenerative neurogenesis. Following photoreceptor ablation, anti-inflammatory treatment suppresses the number of injury-induced progenitors and regenerated photoreceptors. Upon photoreceptor injury, mmp-9 is induced in Müller glia and Müller glia-derived photoreceptor progenitors. Deleting mmp-9 results in over production of injury-induced progenitors and regenerated photoreceptors, but over time the absence of Mmp-9 compromises the survival of the regenerated cones. At all time-points studied, the levels of tnf-α are significantly elevated in mutant retinas. Anti-inflammatory treatment in mutants rescues the defects in cone survival. These data provide a link between injury-induced inflammation in the vertebrate CNS, Mmp-9 function during neuronal regeneration and the requirement of Mmp-9 for the survival of regenerated cones.

Endometriosis is a chronic benign hormone-dependent condition when the endometrial tissue, identical with the endometrium by its morphological and functional properties, grows outside the borders of the uterine mucous membrane. Recent studies have pointed to the possible role of matrix metalloproteinases (MMPs) in the pathogenesis of endometriosis. We suggested a hypothesis that increased expression of MMPs activity in eutopic and ectopic endometrium of patients with endometriosis might correlate with the presence of endometriotic lesions. The aim of the study was to evaluate the level of MMP-2 and MMP-9 expression in the ectopic endometrium of women with visible endometriotic lesions and eutopic endometrium in patients with no signs of endometriosis. The study was conducted on 43 patients. They were divided into two groups. Group 1 included 31 patients with peritoneal/ovarian endometriosis who had undergone laparoscopy and hysteroscopy. Group 2 consisted of 12 patients with leiomyoma, endometrial polyps or relatively healthy patients who had undergone hysterectomy or polypectomy and endometrial curettage. This study showed statistically higher expression of MMP-2 (1.7783 ± 0.22 immunohistochemistry (IHC) optical density score compared to the control group - 1.41± 0.34, p = 0.0017) and MMP-9 (1.352 ± 0.067 versus 1.85 ± 0.26 in the control group, p = 0.001) in ectopic and eutopic endometrium samples from patients with endometriosis compared to samples taken from patients without endometriosis. A strong correlation between expression of the above-mentioned MMPs (r=0.74 for MMP-2 and r=0.88 for MMP-9) in ectopic and eutopic endometrium might be of promising diagnostic value.

Multiple lines of evidence suggest that genetic factors contribute to stroke recovery. The matrix metalloproteinases -2 (MMP-2) and -9 (MMP-9) are modulators of extracellular matrix components, with important regulatory functions in the Central Nervous System (CNS). Shortly after stroke, MMP-2 and MMP-9 have mainly damaging effects for brain tissue. However, MMPs also have a beneficial activity in angiogenesis and neurovascular remodelling during the delayed neuroinflammatory response phase, thus possibly contributing to stroke functional recovery.

Increased lung levels of matrix metalloproteinase 9 (MMP9) are frequently observed during respiratory syncytial virus (RSV) infection and elevated MMP9 concentrations are associated with severe disease. However little is known of the functional role of MMP9 during lung infection with RSV. To determine whether MMP9 exerted direct antiviral potential, active MMP9 was incubated with RSV, which showed that MMP9 directly prevented RSV infectivity to airway epithelial cells. Using knockout mice the effect of the loss of Mmp9 expression was examined during RSV infection to demonstrate MMP9's role in viral clearance and disease progression. Seven days following RSV infection, Mmp9-/- mice displayed substantial weight loss, increased RSV-induced airway hyperresponsiveness (AHR) and reduced clearance of RSV from the lungs compared to wild type mice. Although total bronchoalveolar lavage fluid (BALF) cell counts were similar in both groups, neutrophil recruitment to the lungs during RSV infection was significantly reduced in Mmp9-/- mice. Reduced neutrophil recruitment coincided with diminished RANTES, IL-1β, SCF, G-CSF expression and p38 phosphorylation. Induction of p38 signaling was required for RANTES and G-CSF expression during RSV infection in airway epithelial cells. Therefore, MMP9 in RSV lung infection significantly enhances neutrophil recruitment, cytokine production and viral clearance while reducing AHR.

The present report investigated the correlation between the expression levels of matrix metalloproteinase (MMP)-9 in gastric carcinoma patients and the clinicopathological characteristics. Forty-five samples of gastric carcinoma and distal gastric mucosa tissue, and 10 samples of healthy gastric mucosa tissue were analyzed using semi-quantitative polymerase chain reaction, as well as immunohistochemical and hematoxylin and eosin staining. MMP-9 protein levels in serum samples from the same patients were quantified by enzyme-linked immunosorbent assay. The present report identified that MMP-9 expression was markedly higher in the gastric carcinoma tissue (86.67%) than in the adjacent healthy tissue (10.00%). A positive association was identified between the level of MMP-9 protein expression and the depth of cancer invasion (P<0.05). Furthermore, the preoperative serum levels of the MMP-9 protein in the gastric carcinoma tissue were correlated with the tumor-node-metastasis stage and occurrence of lymph node metastasis (P<0.01). Data from the present report indicates that MMP-9 may be key in gastric carcinoma malignancy, and implies that MMP-9 may serve as a novel biomarker in the diagnosis and prognosis of gastric carcinoma.

Management of neuropathic pain is a real clinical challenge. Despite intense investigation, the mechanisms of neuropathic pain remain substantially unidentified. Matrix metalloproteinase (MMP)-9 and MMP-2 have been reported to contribute to the development and maintenance of neuropathic pain. Therefore, inhibition of MMP-9/2 may provide a novel therapeutic approach for the treatment of neuropathic pain. In this study, we aim to investigate the effect of procyanidins (PC), clinically used health product, on MMP-9/2 in neuropathic pain.

Matrix-metalloproteinases 9 (MMP-9) belongs to the class of matrix metalloproteinases whose main function is to degrade and remodel the extracellular matrix (ECM). MMP-9 has been shown to be an integral part of many diseases where modulation of the ECM is a key step such as cancer, osteoporosis and fibrosis. MMP-9 is secreted as a latent pro-enzyme that requires activation in the extracellular space. Therefore, identifying physiological and molecular contexts, which can activate MMP-9 is important.