Matrix Metalloproteinase-9 In Patients Research Articles

Levels of MMP-9 in patients with intracranial aneurysm: Relation with risk factors, size and clinical presentation

BackgroundIntracranial aneurysms are arterial anomalies affecting 2% to 3% of the general population in the world and these ruptures are associated with a high mortality. Some risk factors, such as age, gender, smoking, alcohol, hypertension and familial history are associated with the number of aneurysms and their size. In addition, inflammatory processes within the blood vessels of the brain can activate matrix metalloproteinase-9 (MMP-9), which degrades various components of the extracellular matrix, such as elastin. Thereby, this work has aimed at evaluating the relationship between plasma MMP-9 levels and the risk factors that are associated with intracranial aneurysm, as well as investigating the aneurysm statuses (ruptured and unruptured) and comparing them with the control volunteers. MethodsBetween August 2014 to June 2016, blood samples were collected from 282 patients (204 ruptured and 78 unruptured saccular intracranial aneurysms) and 286 control volunteers. The MMP-9 plasma levels were measured by ELISA. Statistical analyzes were performed with SPSS software when using parametric or nonparametric tests, after the normality tests. ResultsHigher levels of MMP-9 were found in the aneurysm groups as a whole and when they were stratified by rupture status, then compared with the control group (p < 0.0001). When stratifying them by diameter, those smaller than 7 mm presented high levels of MMP-9 (p < 0.0001), especially in the ruptured ones. As for risk factors, hypertension and smoking were the most important. However, hypertension was mostly associated with the ruptured aneurysms (p < 0.0001). ConclusionsHigh levels of MMP-9 were found in smaller ruptured and unruptured intracranial aneurysms (<7 mm) with strongest statistical associations than other sizes, especially when associated with smoking and hypertension.

Evaluation of matrix metalloproteinase-9 expressions in nasopharyngeal carcinoma patients

Nasopharyngeal carcinoma (NPC) is one of head and neck cancer with a poor prognosis because of the position of the tumor adjacent to the skull base and vital structures. Degradation of extracellular matrix that will cause tumor cells to invade surrounding tissues, vascular or lymphatic vessels. One that plays a role in the extracellular matrix degradation process is matrix metalloproteinase-9 (MMP-9). MMP-9 plays a role in tumor invasion process, metastasis and induction of tumor tissue vascularization. To determine the expression of MMP-9 in patients with nasopharyngeal carcinoma, a descriptive study was conducted by examining immunohistochemistry MMP-9 in 30 NPC tissues that had never received radiotherapy, chemotherapy or combination. Frequency distribution of NPC patient mostly in the age group 41-50 years old and 51-60 years were nine people (30.0%); men (73.3%) and non-keratinizing squamous cell carcinoma (53.3%) histopathology type. The overexpression of MMP-9 in patients with nasopharyngeal carcinoma were mostly found in advance stage.

Left ventricular remodeling and the level of matrix metalloproteinase-9 in patients with coronary artery disease

Left ventricular remodeling and the level of matrix metalloproteinase-9 in patients with coronary artery disease

Serum concentrations of Krebs von den Lungen-6, surfactant protein D, and matrix metalloproteinase-2 as diagnostic biomarkers in patients with asbestosis and silicosis: a case\u2013control study

BackgroundAsbestosis and silicosis are progressive pneumoconioses characterized by interstitial fibrosis following exposure to asbestos or silica dust. We evaluated the potential diagnostic biomarkers for these diseases.MethodsThe serum concentrations of Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and matrix metalloproteinase-2 (MMP-2), MMP-7, and MMP-9 were measured in 43 patients with asbestosis, 45 patients with silicosis, 40 dust-exposed workers (DEWs) without pneumoconiosis, and 45 healthy controls (HCs). Chest high-resolution computed tomography (HRCT) images were reviewed by experts blinded to the clinical data. According to the receiver operating characteristic (ROC) curve, the ideal level of each biomarker and its diagnostic sensitivity were obtained.ResultsThe serum KL-6 and MMP-2 concentrations were highest in patients with asbestosis, particularly in comparison with those in DEWs and HCs (P<0.05). The serum SP-D concentration was significantly higher in patients with asbestosis than in patients with silicosis, DEWs, and HCs (P<0.01), whereas no significant difference was noted among patients with silicosis, DEWs, and HCs. No significant difference in the serum MMP-7 or -9 concentration was found among patients with asbestosis, patients with silicosis, DEWs, or HCs. Among patients with asbestosis, the serum KL-6 concentration was significantly correlated with the lung fibrosis scores on HRCT and negatively correlated with the forced vital capacity (FVC) % predicted and diffusing capacity of the lung for carbon monoxide (DLCO) % predicted. The serum SP-D and MMP-2 concentrations were negatively correlated with the DLCO % predicted (all P<0.05). The order of diagnostic accuracy according to the ROC curve was KL-6, SP-D, and MMP-2 in patients with asbestosis alone and in the combination of both patients with asbestosis and those with silicosis. The combination of all three biomarkers may increase the possibility of diagnosing asbestosis (sensitivity, 93%; specificity, 57%) and both asbestosis and silicosis (sensitivity, 83%; specificity, 62%).ConclusionsKL-6, SP-D, and MMP-2 are available biomarkers for the adjuvant diagnosis of asbestosis and silicosis. The combination of all three biomarkers may improve the diagnostic sensitivity for asbestosis and silicosis.

Potential Involvement of the Epidermal Growth Factor Receptor Ligand Epiregulin and Matrix Metalloproteinase-1 in Pathogenesis of Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease of the nose and paranasal sinuses that presents without or with nasal polyps (CRSwNP). Notable features of CRSwNP are the frequent presence of type 2 allergic inflammation and high prevalence of Staphylococcus aureus (SA) colonization. As inflammation persists, sinus tissue undergoes epithelial damage and repair along with polyp growth, despite active medical management. Because one feature of damaged tissue is enhancement of growth factor signaling, we evaluated the presence of epidermal growth factor receptor (EGFR) ligands and matrix metalloproteinases (MMPs) in CRS. The objectives of this study were to analyze the expression of EGFR ligands and MMPs in patients with CRS and to investigate the possible role of SA on epithelial activation. Sinonasal tissues were collected during surgery from control subjects and patients with CRS. Tissues were processed as described previously for analysis of mRNA (RT-PCR) and proteins (ELISA) for the majority of EGFR ligands within the tissue extracts. CRS tissue was used for evaluation of the distribution of epiregulin (EREG), an EGFR ligand, and MMP-1 by immunohistochemistry. In parallel studies, expression of these genes and proteins was analyzed in cultured primary airway epithelial cells. Elevated expression of EREG and MMP-1 mRNA and protein was observed in uncinate and polyp tissue from patients with CRSwNP. Immunohistochemistry study of clinical samples revealed that airway epithelial cells expressed both of these proteins. Cultured primary human airway epithelial cells expressed MMP-1, and MMP-1 was further induced by stimulation with EREG or heat-killed SA (HKSA). The induction of MMP-1 by HKSA was blocked by an antibody against EREG, suggesting that endogenous EREG induces MMP-1 after stimulation with HKSA. EREG and MMP-1 were found to be elevated in nasal polyp and uncinate tissues in patients with CRSwNP. Elevated expression of EREG and MMP-1 may be related to polyp formation in CRS, and colonization of SA might further enhance this process.

Effects of statins on inflammatory markers and matrix metalloproteinases in patients with ST-segment elevation myocardial infarction

Aim: To evaluate the effects of statins on inflammatory markers and matrix metalloproteinase-1, -3, and -9 in patients with STEMI.

Steroid therapy and renal dysfunction are independently associated with serum levels of matrix metalloproteinase-3 in patients with rheumatoid arthritis

Objective: This study aimed to evaluate whether the level of serum matrix metalloproteinase-3 (MMP-3), a marker of synovium inflammation, is affected by clinical characteristics of patients in rheumatoid arthritis (RA) patients.Methods: We analyzed data from 1087 female patients with RA. Pearson’s correlation coefficients were calculated to explore associations between variables. Stepwise multiple linear regression analysis was performed to evaluate patient background variables that could potentially affect serum MMP-3 levels.Results: Serum MMP-3 was moderately correlated with C-reactive protein (CRP) (r: 0.478). Factors that independently influenced serum MMP-3 levels were CRP (β: 0.450), prednisolone (PSL) use (β: 0.100), estimated glomerular filtration rate (eGFR) (β: −0.085), swollen joint count assessed on 28 joints (β: 0.072), and body mass index (β: −0.061) in female patients with RA. In RA patients with PSL use, factors that independently influenced serum MMP-3 levels were CRP (β: 0.480), eGFR (β: −0.175), and PSL dose (β: 0.171).Conclusions: Our findings suggest that steroid therapy and renal dysfunction affect serum MMP-3 levels in patients with RA.

P-147 - High expression of MMP-9 is associated with better prognosis in extrahepatic bile duct cancer

Introduction: Matrix metalloproteinase-9 (MMP-9) plays an essential role in degrading extracellular matrix and this contributes to invasiveness and metastatic potential of tumor cells. The associations of MMP-9 expression with prognosis in various cancers have been reported in previous studies but there is a controversy about the prognostic role of MMP-9. In this study, we evaluated the prognostic value of MMP-9 in patients with extrahepatic bile duct (EHBD) cancer undergoing surgical resection and adjuvant radiotherapy. Methods: Between January 2000 and August 2006, 66 patients who underwent R0 resection and following adjuvant radiotherapy for EHBD cancer were enrolled in this study. All patients received radiotherapy with median dose of 40 Gy (range, 40-56Gy) and 61 patients received concomitant fluoropyrimidine chemotherapy. Tissue microarray was constructed from surgical specimens of enrolled patients and immunohistochemical staining was undertaken to evaluate the expression of MMP-9. Results: MMP-9 was highly expressed in 33 patients (50.0%). MMP-9 expression was significantly associated with locoregional recurrence-free survival (LRRFS) and overall survival (OS) but not with distant metastasis-free survival (DMFS). The 5-year LRRFS and OS rate were 50.8% versus 86.5% (P = 0.0281), and 23.3% versus 68.1% (P = 0.0087) in patients with low and high expression of MMP-9, respectively. Among the clinicopathologic factors, hilar tumor location was associated with DMFS and OS (p = 0.0292 and p = 0.0003, respectively). Nodal stage and histologic differentiation showed significant association with DMFS (p = 0.0277 and p = 0.0060, respectively). On multivariate analysis for OS, hilar tumor location was the only significant prognostic factor (p = 0.0021), while MMP-9 expression showed marginal significance (p = 0.0633). Conclusion: MMP-9 expression is a favorable prognostic factor for predicting LRRFS and OS in patients with EHBD cancer after surgical resection and adjuvant radiotherapy.

Plasma levels of matrix metalloproteinase 9 in patients undergoing off-pump coronary artery bypass grafting.

Matrix metalloproteinase 9 (MMP9) has recently emerged as a risk predictor in patients with cardiovascular diseases. However, little is known about the significance of increased plasma MMP9 in patients with perioperative myocardial injury. We aimed to investigate the role of MMP9 in the occurrence of myocardial injury during off-pump coronary artery bypass grafting (OPCAB). A total of 34 consecutive patients with coronary artery diseases (CAD) were recruited in this prospective, observational study. All patients were operated for OPCAB surgery. Serial blood samples were collected preoperatively and 12 hours after surgery. MMP9, together with cardiac troponin I (cTnI), creatinine kinase myocardial b fraction (CK-MB), C-reactive protein (CRP), and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in plasma were measured at each time-point. MMP9 levels increased significantly at 12 hours after surgery, attaining nearly 2 times the baseline levels (P=0.0001). There was a significant correlation between preoperative (pre-OP) circulating levels of MMP9 and the left ventricular ejection fraction (LVEF) (r=0.48; P=0.004) as well as European System for Cardiac Operative Risk Evaluation (EuroSCORE) II (r=0.43; P=0.012). Patients were in New York Heart Association (NYHA) functional class III or IV heart failure showed a significantly higher MMP9 levels (1,348.0±337.2 vs. 630.4±93.0 ng/L, P=0.012) as compared to the patients in NYHA functional class I and II. No significant correlation was observed between MMP9 and age (P=0.612), serum creatinine (P=0.185), CRP (P=0.207), NT-proBNP (P=0.058). A significant correlation was observed in these data between the post-OP MMP9 and cTnI (r=0.35; P=0.003). Our study first established a connection between MMP9 and OPCAB procedure, suggesting that MMP9 could be a novel biomarker for identifying perioperative myocardial injury in patients undergoing OPCAB.

The Profile of Circulating Matrix Metalloproteinases in Patients Undergoing Lower Limb Endovascular Interventions for Peripheral Arterial Disease

Matrix metalloproteinases (MMPs) play a significant role in the development and progression of atherosclerotic vascular disease. We aimed to document the profile of circulating MMPs in peripheral arterial disease (PAD) patients undergoing lower limb endovascular revascularization. A total of 46 patients (37 male; mean age 66±11years) undergoing elective lower limb percutaneous revascularization (angioplasty/stent) for symptomatic PAD were recruited from 2 vascular centers. Exclusion criteria were: acute limb ischemia, active infection and/or wet gangrene, liver disease, end-stage renal disease, and cancer. Patients having open revascularization or hybrid (open combined with endovascular) procedures were also excluded. Peripheral venous blood samples were taken on admission and 24hrs after the procedure. Levels of MMP-2, MMP-3, MMP-7, and MMP-9 were measured along with tissue inhibitors of MMPs (TIMPs) 1 and2. Compared to baseline values, there was a significant elevation in serum MMP-3 (P=0.014) and MMP-7 (P=0.008) levels, whereas serum MMP-9 showed a nonsignificant trend to increase (P=0.169). On the other hand, no significant alterations were found 24hrs after angioplasty/stenting with regard to the MMP-2 level and TIMP-1 and 2 levels. This study documented the periprocedural profile of circulating MMPs in patients undergoing angioplasty/stenting for PAD. The implications of increased MMP-3 and MMP-7 activity after peripheral endovascular interventions and their potential clinical relevance require further investigation.

Prognostic role of matrix metalloproteinases in bladder carcinoma: a systematic review and meta-analysis.

Recent studies have shown that matrix metalloproteinases (MMPs) might be a biomarker for predicting outcomes of bladder cancer. However, the prognostic value of overexpression of MMPs in bladder cancer is debatable and the studies are inconsistent. Therefore, this meta-analysis was performed to clarify the specific association and prognostic value of overexpression of MMPs in bladder carcinoma. Relevant studies were identified by searching PubMed, EMBASE, and the Web of Science. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for disease-specific survival (DSS), overall survival (OS), disease/recurrence-free survival (DFS/RFS), and progression/metastasis-free survival (PFS/MFS) were analyzed to determine the prognostic value of MMPs. In total, eighteen applicable studies were included in this meta-analysis. We found that high expression of MMPs significantly correlated with a poor DSS and OS (HR=1.66; 95% CI = 1.38–2.01 and HR= 1.67; 95%CI= 1.26–2.22). MMPs also predicted tumor progression and metastasis with a pooled HR of 3.03 (95% CI 1.98–4.64). However, high MMPs expression had no pivotal impact on DFS/RFS (HR= 1.21; 95% CI= 0.96–1.53). With the purpose of better understanding the prognostic role of MMPs in patients wirh bladder carcinoma, we carried out this systematic review and meta-analysis.

Altered serum level of matrix metalloproteinase-9 and its association with decision-making in eating disorders.

The aims of this study were to determine whether the serum levels of precursor brain-derived neurotrophic factor (proBDNF), mature BDNF (mBDNF), and matrix metalloproteinase-9 (MMP-9) are altered in patients with eating disorders (ED), including anorexia nervosa (AN) and bulimia nervosa (BN), and to explore whether those levels are associated with decision-making abilities. Nineteen women with AN, 28 women with BN, and 22 age-matched healthy control women (HC) were enrolled in the current study. All participants had their decision-making abilities assessed using the Iowa Gambling Task (IGT). Their eating-related pathophysiology and depressive/anxiety symptoms were also evaluated. The MMP-9 level in AN was significantly lower than that in either BN or HC, but the serum levels of proBDNF and mBDNF did not differ among the three groups. Investigation of the serum levels of proBDNF and MMP-9 in patients with ED and controls revealed a significant correlation between them. In the BN, there were positive correlations between mBDNF level and IGT performance and also between MMP-9 level and IGT performance, but these correlations did not occur in AN. The MMP-9 level was positively associated with the Symptom Scale, one of the subscales of the Bulimic Investigatory Test, Edinburgh, only in AN. These results suggest that the serum level of MMP-9 plays a role in the pathophysiology of AN, and both the serum levels of mBDNF and MMP-9 may be associated with decision-making abilities in patients with BN.

Increased Levels of Endothelial Dysfunction Markers and Matrix Metalloproteinases in Patients with Severe Post-Thrombotic Syndrome

Introduction: Post-thrombotic syndrome (PTS) is a common and chronic complication of deep venous thrombosis (DVT) of the lower limbs, which is present in 20% to 50% of patients, and is associated with a high morbidity, low quality of life and significant cost to the healthcare system. Understanding the mechanisms involved in the pathophysiology of PTS may improve the strategies towards disease prevention and treatment. Thus, the aim of the study was to evaluate blood levels of markers of coagulation, inflammation, endothelial dysfunction and matrix metalloproeinases in patients with different grades of PTS severity.Methods: Between January 2012 and May 2015, 31 out 600 consecutive patients with a history of DVT treated at the Hemostasis and Thrombosis Clinic - University of Campinas - Brazil, presented severe PTS and were selected for this study. The presence of PTS was confirmed and classified by Villalta scale. For each patient with severe PTS included in the study, we also included a patient with mild PTS, a patient without PTS, matched by age, gender and time from last DVT, and a healthy control volunteer matched by age and gender. The coagulation markers included FVIII plasma levels evaluated by one-stage clotting assay, and D-dimer by immunoturbidimetric assay. Multiplex analysis was used to determine parameters related to inflammation (IL-1β, IL-6, IL-8, IL-10 and IL-13, MCP-1, TNF-α, RANTES), endothelial dysfunction (thrombomodulin, endothelin-1, sP-selectin, sE-selectin, sICAM-1, sVCAM-1), angiogenic and cell proliferation (EGF, VEGF-C, VEGF-D, TGF-β, PDGF-AA, PDGF-AB/BB) and matrix metalloproteinases and their inhibitors (MMP-1 MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, MMP-13, TIMP-1, TIMP-2). The inflammatory marker C-reactive protein (CRP) was determined by nephelometry.Results: Thirty-one patients with severe PTS were included: 8 male / 23 female, the median age was 51 years and the median time since the last DVT episode occurred was 51 months before the day of the enrollment for the study. The distribution of the groups was similar according to gender, age, ABO blood group, and the time since the last thrombotic episode occurred.Patients with DVT had higher FVIII and D-dimer levels when compared to controls, but there was no difference according to PTS severity.CRP was the only inflammatory marker increased in patients with DVT when compared to controls (0.33 vs. 0.15 mg/L; p = 0.01), and in patients with severe PTS when compared to mild and no PTS (0.40 vs. 0.31 and 0.26 mg/dL; respectively; p=0.04). Regarding endothelial dysfunction markers, our results showed a significant increase of sICAM-1 and thrombomodulin in DVT patients when compared to controls (53.6 vs. 45.5 ng/mL; p≤0,001; 2.16 vs.1.81 ng/mL, p=0.04, respectively), but there was no difference according to the PTS severity. Patients with severe PTS showed increased sE-selectin when compared to patients without PTS (74.74 vs. 68.71 ng/mL; p=0.02). Patients with severe PTS showed increased MMP-7 (8.8 vs. 7.2 ng/mL; p=0.04) and MMP-10 levels (509.3 vs. 394.6 pg/mL; p = 0.04) when compared to patients without PTS. Furthermore, patients with severe PTS showed decreased MMP-9 levels (101.5 vs. 146.4 ng/mL; p=0.04) when compared to mild PTS. There was no difference in the parameters associated to angiogenesis (VEGF, endotelin-1, EGF) or cell proliferation (TGF-β, PDGF-AA, PDGF-AB/BB) between the groups.Discussion and Conclusions: The results may support the association of coagulometric, inflammatory and endothelial processes in severe PTS, in a well-defined cohort of patients with severe PTS. Previous studies in animal models have shown that matrix metalloproteinases have an important role in the resolution of venous thrombus, and this process leads to changes in vein wall. Our results are consistent with this finding, once we observed increased blood levels of MMPs and markers of endothelial dysfunction/activation in patients with DVT, especially those with severe PTS. We speculate that matrix metalloproteinases can play an important role in the development of severe PTS, culminating in a chronic endothelial dysfunction of the affected limb. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The role of serum levels of microRNA-21 and matrix metalloproteinase-9 in patients with acute coronary syndrome.

Acute coronary syndrome (ACS) is one of the leading causes of cardiovascular death. It seems that microRNA-21 and matrix metalloproteinase-9 implicated in the pathogenesis of cardiovascular diseases. The aim of this study was to investigate the role of circulating miR-21 and MMP-9 as biomarkers for ACS. Based on coronary angiography and electrocardiography results, 50 patients with ACS and 50 patients with stable coronary artery disease (stable CAD) were enrolled in this study. Samples were collected from patients and stored at -80°C. Serum miR-21 gene expression was measured by quantitative real-time PCR method. Serum total MMP-9 was measured by enzyme-linked immunosorbent assay kit. Also, the activity of MMP-9 was measured by gelatin zymography. Patients with ACS had a significantly higher miR-21 level compared to the stable CAD ([Formula: see text]=0.88±0.06 and 0.31±0.08 respectively, P<0.001). At the same time, the serum levels and activity of MMP-9 were significantly higher in ACS patients compared to those with stable CAD (324.01±17.57 and 204.6±12.39ng/mL, P<0.001, and 2524.5±131.3 and 1280.8±19.6 units, P<0.001, respectively). miR-21 expression levels were correlated positively with MMP-9, hs-CRP, and age and negatively with HDL-cholesterol (r=0.33, P<0.001, r=0.22, P<0.031, r=0.26, P<0.008, r=-0.32, P<0.001, respectively). We concluded that increased serum expression of miR-21 and higher serum activity of MMP-9 may be useful indicators for ACS. However, we suggest further studies to be performed.

Omentin concentrations are independently associated with those of matrix metalloproteinase-3 in patients with mild but not severe rheumatoid arthritis.

Omentin is an adipokine that reportedly protects against cardiometabolic risk. We investigated the relationships between omentin concentrations and subclinical cardiovascular disease in rheumatoid arthritis (RA). Omentin concentrations were measured in 213 (104 black; 109 white) RA patients. Relationships of omentin levels with those of endothelial activation markers, ultrasound determined carotid intima-media thickness and plaque, and matrix metalloproteinase (MMP)-2, -3 and -9 that mediate altered plaque stability, were identified in confounder adjusted multivariate regression models. Omentin concentrations were inversely associated with MMP-3 levels [β=-364 (0.113), p=0.002]. This relationship was influenced by population origin, RA activity and the erythrocyte sedimentation rate and joint deformity count (interaction p value=0.009, 0.04, 0.04 and 0.007, respectively). Accordingly, the omentin-MMP-3 concentration relationship was reproduced in white [β (SE)=-0.450 (0.153), p=0.0004)] but not black patients [β (SE)=-0.099 (0.195), p=0.6)], in participants with disease remission or mild disease activity [β (SE)=-0.411 (0.139), p=0.004] but not with moderate or severe RA activity [β (SE)=-0.286 (0.202), p=0.2], and in those with a small [β (SE)=-0.534 (0.161), p=0.001] but not large erythrocyte sedimentation rate [-0.212 (0.168), p=0.2] and without [β (SE)=-0.554 (0.165), p=0.0001] but not with large joint deformity counts [-0.110 (0.173), p=0.5]. Omentin levels were unrelated to endothelial activation and atherosclerosis. Among patients with RA, a lack of plaque stabilizing effects by omentin may contribute to the reported link between severe disease and increased cardiovascular risk. The association between concentrations of omentin and MMP-3 is population specific in RA.

Stress-induced release of matrix metalloproteinase-9 in patients with coronary artery disease: The possible influence of cortisol

Stress and inflammation are both important risk factors for coronary artery disease (CAD). However, the susceptibility to stress-induced inflammation and its determinants have been little explored in patients with CAD. Here, our aim was to study the stress-induced inflammatory response, more precisely the early release of matrix metalloproteinase (MMP)-9, and its association with cortisol response in patients with CAD. Sixty-four patients underwent a standardized laboratory stress test. The stress-induced release of MMP-9 was closely associated with the release of other neutrophil-associated proteins, MMP-8 and myeloperoxidase (MPO). It also showed a large variation among patients, as did cortisol. Twenty minutes after stress, a negative association between changes in MMP-9 and cortisol was seen (p<0.01). In vitro, dexamethasone reduced the IL-8-mediated release of MMP-9 from neutrophils, indicating that glucocorticoids may exert rapid effects on neutrophil activation. Further characterization of patients revealed that stress-induced release of MMP-9 was related to leukocyte telomere shortening and increased ultrasound-assessed plaque occurrence in the carotid arteries, but not to other characteristics such as age, gender or psychological background factors. The susceptibility to stress-induced release of MMP-9 may thus have impact on disease phenotype. Stress tests can be useful to identify CAD patients in need of novel prevention and treatment strategies.

Evaluation of physiological risk factors, oxidant-antioxidant imbalance, proteolytic and genetic variations of matrix metalloproteinase-9 in patients with pressure ulcer.

Pressure ulcer (PU) remains a common worldwide problem in all health care settings, it is synonymous with suffering. PU is a complex disease that is dependent on a number of interrelated factors. It involves multiple mechanisms such as physiological risk factors, chronic inflammation, oxidant–antioxidant imbalance and proteolytic attack on extracellular matrix by matrix metalloproteinases (MMP). Therefore, we propose that these wounds lead to molecular variations that can be detected by assessing biomarkers. In this study, we aimed to evaluate the major clinical elements and biological scars in Tunisian patients suffering from PU. Consistently, non-healing wound remains a challenging clinical problem. The complex challenges of the wound environment, involving nutrient deficiencies, bacterial infection, as well as the critical role played by inflammatory cells, should be considered because of their negative impact on wound healing. In addition, an imbalance between pro-oxidants and antioxidant systems seems to be more aggravated in patients with PU compared to healthy subjects. Of interest, this study provides further evidence to support a core role of the biological activity of MMP-9 in the pathogenesis of PU and indicates that the MMP9-1562 C/T (rs 3918242) functional polymorphism is associated with protection against this disease.

Plasma Matrix Metalloproteinases in Patients With Stroke During Intensive Rehabilitation Therapy

ObjectiveTo study plasma levels of matrix metalloproteinases (MMPs) as potential markers of recovery during intensive rehabilitation therapy (IRT) after stroke. DesignProspective and descriptive 3-month follow-up study. SettingRehabilitation unit and research center. ParticipantsPatients with first-ever ischemic stroke (n=15) enrolled to IRT (≥3h/d and 5d/wk) and healthy volunteers (n=15) (N=30). InterventionsNot applicable. Main Outcome MeasuresThe primary outcome was to measure plasma MMP3, MMP12, and MMP13 levels and evaluate potential associations with motor/functional scales using a battery of tests (National Institutes of Health Stroke Scale, modified Rankin scale, Barthel Index, Fugl-Meyer Assessment, Functional Ambulation Categories, Medical Research Council scale, Chedoke Arm and Hand Activity Inventory, and the 10-m walk test) before IRT and at 1- and 3-month follow-ups. The secondary outcome was to evaluate the use of these MMPs as biomarkers as predictors of patient's outcome. ResultsMMP levels remained stable during the study period and were similar to those in the healthy volunteer group. However, baseline MMP12 and MMP13 levels were strongly associated with stroke severity and were found to be elevated in those patients with the poorest outcomes. Interestingly, plasma MMP3 was independent of baseline stroke characteristics but was found to be increased in patients with better motor/functional recovery and in patients with larger improvements during rehabilitation. ConclusionsMMPs might act as biologic markers of recovery during rehabilitation therapy related to their roles in both injury and tissue remodeling. Future confirmatory investigations in multicenter studies are warranted by our data.

Influence of Rosuvastatin on Blood Lipids, Inflammatory Factors, Oxidative Stress and Matrix Metalloproteinases in Patients with Chronic Heart Failure

Influence of Rosuvastatin on Blood Lipids, Inflammatory Factors, Oxidative Stress and Matrix Metalloproteinases in Patients with Chronic Heart Failure

Alteration of matrix metalloproteinase-3 O-glycan structure as a biomarker for disease activity of rheumatoid arthritis.

BackgroundNearly all secreted proteins are glycosylated, and serum glycoproteins that exhibit disease-associated glycosylation changes have potential to be biomarkers. In rheumatoid arthritis (RA), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) are widely used as serologic biomarkers, but they lack sufficient specificity or precision. We performed comparative glycosylation profiling of MMP-3 using a recently developed antibody-overlay lectin microarray technology that allows semicomprehensive and quantitative analysis of specific protein glycosylation to develop an RA-specific disease activity biomarker.MethodsSerum was taken from patients with RA (n = 24) whose disease activity was scored using composite measures, and MMP-3 was immunoprecipitated and subjected to lectin microarray analysis. A disease activity index (DAI) based on lectin signal was developed and validated using another cohort (n = 60). Synovial fluid MMP-3 in patients with RA and patients with osteoarthritis (OA) was also analyzed.ResultsIntense signals were observed on a sialic acid-binding lectin (Agrocybe cylindracea galectin [ACG]) and O-glycan-binding lectins (Jacalin, Agaricus bisporus agglutinin [ABA], and Amaranthus caudatus agglutinin [ACA]) by applying subnanogram levels of serum MMP-3. ACG, ABA, and ACA revealed differences in MMP-3 quantity, and Jacalin revealed differences in MMP-3 quality. The resultant index, ACG/Jacalin, correlated well with disease activity. Further validation using another cohort confirmed that this index correlated well with several DAIs and their components, and reflected DAI changes following RA treatment, with correlations greater than those for MMP-3 and CRP. Furthermore, MMP-3, which generated a high ACG/Jacalin score, accumulated in synovial fluid of patients with RA but not in that of patients with OA. Sialidase digestion revealed that the difference in quality was derived from O-glycan α-2,6-sialylation.ConclusionsThis is the first report of a glycoprotein biomarker using glycan change at a local lesion to assess disease activity in autoimmune diseases. Differences in the degree of serum MMP-3 α-2,6-sialylation may be a useful index for estimating disease activity.