Value Of Matrix Metalloproteinase-9 Research Articles

Fluid-Attenuated Inversion Recovery Hyperintensity Correlates With Matrix Metalloproteinase-9 Level and Hemorrhagic Transformation in Acute Ischemic Stroke

Matrix metalloproteinase-9 (MMP-9) is elevated in patients with acute stroke who later develop hemorrhagic transformation (HT). It is controversial whether early fluid-attenuated inversion recovery (FLAIR) hyperintensity on brain MRI predicts hemorrhagic transformation (HT). We assessed whether FLAIR hyperintensity was associated with MMP-9 and HT. We analyzed a prospectively collected cohort of acute stroke subjects with acute brain MRI images and MMP-9 values within the first 12 hours after stroke onset. FLAIR hyperintensity was measured using a signal intensity ratio between the stroke lesion and corresponding normal contralateral hemisphere. MMP-9 was measured using enzyme-linked immunosorbent assay. The relationships between FLAIR ratio (FR), MMP-9, and HT were evaluated. A total of 180 subjects were available for analysis. Patients were imaged with brain MRI at 5.6±4.3 hours from last seen well time. MMP-9 blood samples were drawn within 7.7±4.0 hours from last seen well time. The time to MRI (r=0.17, P=0.027) and MMP-9 level (r=0.29, P<0.001) were each associated with FR. The association between MMP-9 and FR remained significant after multivariable adjustment (P<0.001). FR was also associated with HT and symptomatic hemorrhage (P=0.012). FR correlates with both MMP-9 level and risk of hemorrhage. FLAIR changes in the acute phase of stroke may predict hemorrhagic transformation, possibly as a reflection of altered blood-brain barrier integrity.

A systematic review of matrix metalloproteinase 9 as a biomarker of survival in patients with osteosarcoma

Matrix metalloproteinase 9 (MMP-9) plays an important role in the progression of several types of cancer by increasing tumor growth, migration, invasion, and metastasis and is associated with poor disease prognosis. The possible prognostic value of MMP-9 in osteosarcoma has also been examined, but due to inconsistent results between studies, it has not been possible to draw firm conclusions. To clarify this issue, we conducted a meta-analysis of published studies to provide a comprehensive evaluation of the effect of high MMP-9 expression on the survival outcomes of osteosarcoma patients. Seven studies with a total of 339 patients with osteosarcoma were examined. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to evaluate the effect of MMP-9 expression on overall survival. Meta-analysis showed that patients with high MMP-9 expression were significantly associated with lower overall survival when compared to their counterparts with low or undetectable MMP-9 expression (OR=6.13, 95 % CI 3.45-10.89, P<0.001). Sensitivity analysis suggested the pooled OR was stable and not significantly changed when a single study was removed. The results from the systematic review and meta-analysis show that MMP-9 is an effective biomarker for predicting survival of patients with osteosarcoma.

Changes in serum levels of MDA and MMP-9 after UPF in patients with OSAS

The aim of the study was to assess the markers of oxidant-antioxidant status in patients with obstructive sleep apnea syndrome (OSAS) who underwent uvulopalatal flap (UPF) surgery. Twenty-five patients who underwent UPF surgery participated in this study. Polysomnographic examinations were performed before and after the surgery to assess sleep apnea in all patients and to determine the success of the UPF surgery regarding the improvement in the apnea-hypopnea index (AHI). Descriptive factors (BMI, age, gender and neck thickness, etc.) of patients were recorded before operation. Blood samples were taken preoperatively, and repeated postoperatively at 6-month intervals to determine the changes in serum malondialdehyde (MDA) and matrix metalloproteinase-9 (MMP-9) levels. The mean age at surgery was 45.6±9.9years (range 25-63years). There was a significant difference between preoperative and postoperative AHI, MDA and MMP-9 values (p<0.05). There was no significant correlation between categorical variables. There was no correlation between postoperative ODI, MMP-9 and MDA. These results indicate that OSAS is associated with abnormal lipid peroxidation, which can be improved by UPF surgery. OSAS may increase risks of cardiovascular morbidity; however, UPF might be useful for decreasing these risks in patients with OSAS who are suitable candidates for UPF surgery.

Evaluation of Serum Levels of HER2, MMP-9, Nitric Oxide, and Total Antioxidant Capacity in Egyptian Breast Cancer Patients: Correlation with Clinico-Pathological Parameters

Breast cancer is by far the most common cancer in women worldwide and the main cause of cancer-related mortality. Breast cancer accounts for 38% of all malignancies among Egyptian women. The aim of our study was to evaluate the serum levels of human epidermal growth factor receptor-2 (HER2), matrix metalloproteinase-9 (MMP-9), nitric oxide (NO), and total antioxidant capacity (TAC) in breast cancer patients and to correlate these markers with clinico-pathological parameters. Serum HER2, MMP-9, and carcinoma antigen 15-3 (CA 15-3) were assessed in 80 breast cancer patients and ten healthy subjects as a control group by the enzyme-linked immunosorbent assay (ELISA) technique while NO and TAC were assessed by a colorimetric method. Serum HER2 was ≥15 ng/mL in nine patients (11.3%). High HER2 ECD levels were significantly associated with tissue HER2 (P<0.0001), metastasis (P= 0.0024), and negativity of both estrogen (P=0.0075) and progesterone (P=0.0239) receptors. Serum MMP-9 (P=0.0013), NO (P<0.0001), and CA 15-3 (P<0.0001) were significantly increased while serum TAC was significantly (P=0.01) decreased in breast cancer patients as compared to the control group. Serum MMP-9 was increased significantly (P=0.028) in metastatic patients as compared to non-metastatic patients. We found a positive correlation between serum HER2 and CA 15-3 (r=36, p=0.005). In conclusion, serum HER2 reflects the tissue HER2 status of breast cancer, so the determination of serum HER2 is helpful in assessing HER2 status, but in addition, a high level may reflect metastatic disease. Also, serum MMP-9 can be useful for denoting the development of metastasis in breast cancer patients. Follow-up is needed to evaluate the value of serum HER2 and MMP-9 as prognostic markers.

Prognostic Value of MMP-9 in Ovarian Cancer: A Meta-analysis

Matrix metalloproteinase-9(MMP-9) plays an important role in tumor cell invasion. Although it has been studied frequently in ovarian cancer, its prognostic impact is still equivocal. The aim of this study was to more precisely estimate its prognostic significance. We searched Pubmed, Embase, OVID, Sciencedirect and CBM databases to identify eligible studies. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were pooled across studies using fixed-effects or random-effects models. We also performed subgroup analysis. 30 studies (n=2552 patients) focusing on prognosis or expression of MM-9 were included. Increased expression of MMP-9 was associated with poor prognosis in ovarian cancer patients (HR=1.68, 95%CI 1.09-2.59, p=0.02). Besides, MMP-9 expression in ovarian cancer was significantly higher than non-malignant tumors (OR=11.46, 95%CI 8.47-15.50, P<0.00001). Moreover, increased expression of MMP-9 was significantly associated with FIGO stage (OR=4.85, 95%CI 2.60-9.04, P<0.00001), grade of differentiation (OR=3.34, 95%CI 2.46-4.54, P<0.00001), lymph node metastasis (OR=5.75, 95%CI 3.71-8.92, P<0.00001) and there was no association with histological type of ovarian cancer. Increased expression of MMP- 9 was associated with poor prognosis in ovarian cancer patients. Down-regulation of MMP-9 is an attractive therapeutic approach which might improve outcome of ovarian cancer.

Inverse correlation between Naa10p and MMP-9 expression and the combined prognostic value in breast cancer patients

To analyze the expression profiles of N-a-acetyltransferase 10 protein (Naa10p/ARD1) and matrix metalloproteinase 9 (MMP-9) in human breast cancer and evaluate their possible prognostic values in breast cancer patients. Quantitative RT-PCR was used to evaluate mRNA expression of Naa10p and MMP-9 in 55 cases of fresh breast cancer tissues, and immunohistochemistry was performed for detecting Naa10p and MMP-9 proteins on breast cancer with tissue microarray containing 80 specimens. Furthermore, Naa10p and MMP-9 were measured in 253 breast cancer tissues from patients with up to 15-year follow-up. Survival curves were generated using the Kaplan-Meier method. Multivariate analysis was performed by using the Cox proportional hazard regression model to assess the prognostic values of Naa10p and MMP-9. Both Naa10p and MMP-9 expression in breast cancer tissues were significantly higher than those in the matched non-cancerous tissues (p = 0.000 for both). There was an inverse correlation between Naa10p and MMP-9 expression at mRNA and protein levels (p = 0.000 for both). Patients with MMP-9- positive expression had a poorer overall survival (OS) and disease-free survival (DFS) than those with MMP-9-negative expression (p = 0.001 for both). However, patients with Naa10p-positive expression had better OS and DFS (p = 0.000 for both). In addition, Naa10p-positive/MMP-9- negative patients had the best OS and DFS (p = 0.000 for both). In multivariate survival analysis, TNM stage, Naa10p expression, MMP-9 expression, and combined expression status of Naa10p/MMP-9 were independent prognostic factors related to OS (p = 0.000, 0.007, 0.012, and 0.000, respectively) and DFS (p = 0.000, 0.002, 0.014, and 0.000, respectively).The expression level of Naa10p was inversely correlated with that of MMP-9 in human breast cancer samples. Combined analysis of Naa10p and MMP-9 had a significantly increased value for determining the prognosis of breast cancer patients.

Prognostic value of biological markers in myocardial infarction patients

The aim of this study was to compare the prognostic value of matrix metalloproteinase-3 and -9, and NT-pro-natriuretic peptide for fatal and nonfatal complications in Q-wave myocardial infarction patients in the acute and postinfarction periods. 85 men and women with documented Q-wave myocardial infarction were observed for 1 year after hospitalization. Clinical endpoints were identified through the hospital patient-tracking system, with a review of medical records for each recorded endpoint. Left ventricular ejection fraction and wall motion index were calculated. Measurements of matrix metalloproteinases and NT-pro-natriuretic peptide were performed by an enzyme-linked immunosorbent assay. A cutoff value of 9.7 ng·mL(-1) for matrix metalloproteinase-3 showed the best discriminatory power (sensitivity = 77.8%, specificity = 90.8%). The optimal cutoff value of matrix metalloproteinase-9 was 18.1 ng·mL(-1) (sensitivity, 70.5%; specificity, 75%), and the cutoff for NT-pro-natriuretic peptide was 885 pmol·L(-1) (sensitivity, 58%; specificity, 68.6%). Matrix metalloproteinase-3 and -9 were strongly related with a positive prognostic value of 70% (sensitivity and specificity, 84% and 82%, respectively). These data may be helpful for further stratification of patients into cardiovascular mortality risk groups.

The value of matrix metalloproteinase-9 and vascular endothelial growth factor receptor 1 pathway in diagnosing indeterminate pleural effusion†

Our aim was to determine the diagnostic value of the matrix metalloproteinase-9/vascular endothelial grow factor receptor-1 pathway in differentiating pleural effusions (PE) of varying origin. In the last two years, 55 consecutive patients with exudative PE have been enrolled. In all patients, we measured PE levels of vascular endothelial grow factor receptor-1 (VEGFR-1) in soluble form, through enzyme-linked immunosorbent assay (ELISA) (results expressed in pg/ml) and western blot, and of matrix metalloproteinase-9 (MMP-9), through ELISA (results expressed in ng/ml). The values recorded were then statistically compared with the etiologic diagnosis of the PEs. Between the PEs analysed, 40 were found to be malignant and 15 to be benign. VEGFR-1 in soluble form (sVEGFR-1) was significantly higher in malignant than in benign effusions (P < 0.0001), using ELISA; the same was shown by the western blot analysis method. MMP-9 levels results also indicated significantly more malignant than benign effusions (P < 0.0001). VEGFR-1 in soluble form showed a sensitivity and specificity of 92% and 93%, respectively, (cut-off value >852; AUC: 0.9) in predicting the malignant nature of a PE. Sensitivity and specificity of MMP-9 in predicting the malignant nature of a PE were, respectively, 95% and 73% (cut-off value >639; AUC: 0.8). In the pleural fluids, the values of the two markers were significantly related to each other (r = 0.5; P < 0.0001). Eighteen patients with malignancies, diagnosed by pleural biopsy, had negative cytological findings. Of these patients, sixteen (89%) presented elevated levels of both markers. Our data suggest that the VEGFR-1/MMP-9 pathway is significantly increased in malignant-rather than in benign-pleural effusions; thus, the measurement of their levels in the pleural effusion could be useful, throughout the diagnostic work-up, to select which cases would warrant a pleural biopsy.

Values of matrix metalloproteinase-9 in early diagnosis and short-term prognosis of ST-segment elevation myocardial infarction

To evaluate the early diagnostic value of matrix metalloproteinase-9 (MMP-9) level on admission for ST-segment elevation myocardial infarction (STEMI), explore the relationship between MMP-9 and global registry of acute coronary events (GRACE) scores and determine the values of MMP-9 in short-term prognosis of STEMI. A total of 55 STEMI patients admitted into our hospital between September 2011 and February 2012 were recruited. There were early STEMI (≤ 4h of onset, n = 22) and late STEMI (> 4 h after onset, n = 33). Fifty subjects of coronary artery without significant stenosis after angiography were enrolled into a control group. The plasma levels of MMP-9 in venous blood were detected with enzyme-linked immunosorbent assay (ELISA). And the GRACE risk score was used for risk assessment. The incidence of new or recurrent myocardial infarction, target vessel revascularization, cardiac death, heart failure (MACE) was recorded during a follow-up period of 6 months. The MMP-9 levels were significantly higher in patients with STEMI (P < 0.001), early STEMI (P < 0.001) and late STEMI (P < 0.001) than the control group. And no statistical differences existed between early STEMI and late STEMI (P > 0.05). The level of MMP-9 was positively correlated with the GRACE risk score. MACE occurred in 8 [14.5% (8/55)] patients during hospitalization and 17 [30.9% (17/55)] patients during follow-up. Receiver operating characteristic (ROC) curve analysis showed area under the curve (AUC) of on admission GRACE risk score and MMP-9 levels were 0.848 (95%CI 0.706 - 0.991, P = 0.002) and 0.766 (95%CI 0.575 - 0.957, P = 0.017) respectively. ROC curve analysis showed AUC of hospital discharge GRACE risk score and MMP-9 levels were 0.737 (95%CI 0.601 - 0.873, P = 0.005) and 0.711 (95%CI 0.565 - 0.856, P = 0.013) respectively. No statistical differences existed between GRACE risk score and MMP-9 levels for predicting the short-term risk of MACE (P > 0.05). The plasma level of MMP-9 has a higher diagnostic value for early STEMI. Positively correlated with the GRACE risk score, it is a predicator of short-term risk of MACE.

Matrix Metalloproteinase-9 (MMP-9) and Myeloperoxidase (MPO) Levels in Patients with Nonobstructive Coronary Artery Disease Detected by Coronary Computed Tomographic Angiography

The aim of this study was to evaluate whether matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) are elevated in patients with nonobstructive coronary artery disease. Eighty-four patients with nonobstructive coronary artery disease (group A) and 90 patients with no coronary plaques (group B) were enrolled. MMP-9 and MPO levels were compared between the two groups. The relationships between these biomarkers and Framingham risk score were analyzed. Receiver-operating characteristic curves were used to evaluate the ability of these biomarkers to predict the presence of coronary artery plaques. The MMP-9 and MPO values in group A were significantly higher than in group B (P < .001). The levels of MMP-9 and MPO showed significant correlations with Framingham risk score (r = 0.796, P < .001, and r = 0.409, P < .001, respectively). The areas under the receiver-operating characteristic curves for MMP-9 and MPO were 0.80 (95% confidence interval, 0.74-0.87) and 0.74 (95% confidence interval, 0.66-0.81), respectively. Levels of MMP-9 and MPO are positively correlated with Framingham risk score. Additionally, in patients with nonobstructive coronary artery disease, elevated levels of MMP-9 and MPO may identify patients at risk for future myocardial infarction or sudden cardiac death.

Urinary Matrix Metalloproteinase Activity in Diabetic Kidney Disease: A Potential Marker of Disease Progression

Background: Progressive kidney fibrosis, associated with chronic kidney disease (CKD), results from an imbalance in extracellular matrix (ECM) homeostasis. Reduced matrix metalloproteinases (MMP) activity causing lower clearance of ECM proteins has been implicated mainly through an overproduction of tissue inhibitors of metalloproteinases (TIMP), but also by reduced MMP synthesis. We tested the hypothesis that MMP activity can be measured in human urine and can be used as a potential biomarker of the progression of diabetic kidney disease (DKD). Methods: An observational prospective study was performed on 102 DKD patients using 21 diabetic patients without kidney disease and 21 healthy volunteers as controls. The Molecular Probes EnzChek Gelatinase/Collagenase Assay Kit were used to determine urinary MMP activity using DQ™ Gelatin (total MMPs), DQ™ Collagen I (interstitial collagenases) and DQ™ Collagen IV (gelatinises) substrates. A broad-spectrum synthetic inhibitor of all MMP, 1,10-phenanthroline, was used to confirm that the proteolytic activity is due to MMP activity. All MMP values were expressed per unit of urine creatinine. Results: Overall urinary MMP activity (DQ Gelatin substrate) was significantly elevated in DKD patients (14.76 ± 3.65 Δ fl/h/mmol creatinine) compared to diabetes mellitus controls (7.09 ± 2.12 Δ fl/h/mmol creatinine) and healthy volunteers (1.87 ± 0.74 Δ fl/h/mmol creatinine) (ANOVA p = 0.01). Within the DKD cohort, there was an approximate threefold higher urinary MMP activity in nonprogressive DKD patients compared to those with progressive disease (p = 0.002). The urinary MMP activity:creatinine ratio was significantly higher in normoalbuminuric and microalbuminuric DKD compared to macroalbuminuric DKD. Positive correlations were observed between the rate of total MMP activity and interstitial collagenases (r = 0.75, p < 0.0001) and gelatinases (r = 0.59, p = 0.0001). The accuracy of MMP activity to predict the rate of annual eGFR decline (ROC analysis) was 77% compared to 64% for albuminuria. Conclusions: Total MMP activity can be easily measured in human urine. Surprisingly and in contrast to MMP activity in the kidney, urine MMP activity is elevated in DKD. However, there is a significantly lower MMP activity in patients with progressive DKD. ROC analysis demonstrates that single urine MMP activity estimation is superior to albuminuria in predicting DKD patients with progressive disease.

Nazal polipli hastalarda serum matriks metalloproteinaz-9 seviyelerinin hastalığın etiyopatogenezindeki rolü

Objective: The aim of this study is to reveal the role of matrix metalloproteinase-9 in the pathogenesis of nasal polyps by comparing its levels in normal healthy subjects, and patients with nasal polyps. Our second aim is to demonstrate the correlation (if any) between white blood cell counts, age, gender of the patients presence of asthma, and MMP-9 levels. Methods: Serum samples of patients were obtained and kept at -70°C. Quantikine kit (R&D System Inc, Minneapolis, MN, USA) micro-ELISA (Enzyme-Linked Immunosorbent Assay) method was used to estimate plasma matrix metalloproteinase-9 levels. Serum matrix metalloproteinase-9 values of the control, and the patient groups were compared. The correlation between age, gender of the study subjects, white blood cell counts and the presence of asthma was investigated. Results: Serum matrix metalloproteinase-9 values were significantly higher in patients with nasal polyps relative to the control group. White blood cell counts in the group with nasal polyps were higher without any statistically significant difference between the groups. Any correlation between matrix metalloproteinase-9 values, age, and gender was not found. In addition, any correlation was not detected between concomitant asthmatic disease and matrix metalloproteinase-9 values. Conclusion: Significantly, higher matrix metalloproteinase-9 values in patients with nasal polyps support our opinion suggesting the role of this protein in the etiopathogenesis of this disease.

Plasma metalloproteinase-9 and restrictive filling pattern as major predictors of outcome in patients with ischemic cardiomyopathy

ObjectiveAssessment of plasma matrix metalloproteinase-9 (MMP-9) and Doppler markers of increased left ventricular (LV) filling pressure may be added to risk stratify patients with ischemic cardiomyopathy (IC). Therefore, we aimed at investigating the value of plasma MMP-9 and restrictive filling pattern (RFP) in IC patients. MethodsEighty-eight consecutive patients hospitalized for heart failure (LV ejection fraction≤40%) due to IC were enrolled. A complete M-mode and two-dimensional echo-Doppler examination were performed. Patients were defined as having RFP if they had a mitral E wave deceleration time<150ms. Plasma MMP-9 and N-terminal protype-B natriuretic peptide levels were assessed at the time of the index echocardiogram. The end point was all-cause mortality or hospitalization for worsening HF. Follow-up period was 25±17months. ResultsMedian value of MMP-9 was 714ng/ml. On univariate analysis, a number of measurements predicted the composite end point: NYHA class>2, RFP, MMP-9>60.5ng/ml, LV ejection fraction<27%, anemia, pulmonary pressure≥35mmHg, N-terminal protype-B natriuretic peptide>1742pg/ml, and glomerular filtration rate<60ml/min/1.73m2. Independent variables of outcome were anemia (HR=1.9, p=0.031), and the combination of plasma MMP-9 and RFP (HR=3.2, p=0.004). On Kaplan–Meier survival curves, patients with elevated MMP-9 levels and RFP had the lowest event-free survival rate (log-rank: 29.0, p<0.0001). The net reclassification improvement showed a significant increase in the prediction model when elevated MMP-9 and RFP were added to the base model that included clinical, biochemical and echocardiographic parameters (p<0.0001). ConclusionMMP-9 levels and RFP have an incremental predictive value to risk classify IC patients.

Anticoagulants affect matrix metalloproteinase 9 levels in blood samples of stroke patients and healthy controls

Matrix metalloproteinase-9 (MMP-9) represents a promising marker for acute stroke management. In clinical studies MMP-9 has been quantified by ELISA using differing protocols. We aimed to establish a valid protocol by evaluation of preanalytics. Blood from stroke patients (n=28) and healthy controls (n=28) was drawn into tubes containing different anticoagulants (EDTA, citrate, lithium-heparin (heparin) and heparin with proteinase inhibitors) and processed after 0, 60 and 240 min. MMP-9 plasma protein and mRNA from mononuclear leukocytes were determined. In regard to anticoagulants used, samples showed different MMP-9 protein baseline values and kinetics. Stable MMP-9 protein concentrations were only measured from EDTA samples. Particularly in samples with proteinase inhibitors protein and mRNA concentrations increased over time. Kinetics did not differ between patients and controls. Preanalytics plays a key role for determination of MMP-9. EDTA seems to be a valid anticoagulant for MMP-9 protein measurement.

Identification of Factors Causing Sudden Coagulation in Patients with Acute Myocardial Infarction

Background: Coronary artery disease (CAD) evolving to acute myocardial infarction (AMI) is due to the thrombotic occlusion of coronary vessels in the presence of destabilized atheroma, rich in inflammatory cells secreting proteolytic enzymes that induce the development of thrombosis. The aim of this study was to analyse the plasma of AMI patients for the detection of proteases or factors that may cause fast coagulation. Methods: The patients were analysed for the presence in plasma of cardiac troponin T (c-TnT) or proteases as neutrophil gelatinase-associated lipocalin (NGAL) using ELISA method and matrix metalloproteinase-9 (MMP-9) utilising flow cytometry technique and interleukin-8 (IL-8) using flow cytometry methodology. Results: The presence of AMI was demonstrated by high levels of c-TnT; in comparison with controls the AMI patients displayed a significant increase in the values of MMP-9 and low levels of antithrombin III: these markers were negatively correlated: MMP-9 appeared to cause the coagulation activity documented by the consumption of antithrombin III. The same patients also showed high levels of NGAL, which is known to modulate MMP-9 activity and to be involved in coagulation process: patients also exhibited an increased amount of IL-8 which appears to be associated with high levels of NGAL: this cytokine seems to affect the values of NGAL which is linked to coagulation process. Conclusion: The high levels of MMP-9, NGAL and IL-8 in AMI patients seemed to be interrelated and connected with the process leading to rapid coagulation. These markers may be measured in absence of AMI, particularly in CAD patients, as their detection may reveal a risk of sudden coronary coagulation.

Matrix metalloproteinase 9 and cellular fibronectin plasma concentrations are predictors of the composite endpoint of length of stay and death in the intensive care unit after severe traumatic brain injury.

BackgroundThe relationship between severe traumatic brain injury (TBI) and blood levels of matrix metalloproteinase-9 (MMP-9) or cellular fibronectin (c-Fn) has never been reported. In this study, we aimed to assess whether plasma concentrations of MMP-9 and c-Fn could have predictive values for the composite endpoint of intensive care unit (ICU) length of stay (LOS) of survivors and mortality after severe TBI. Secondary outcomes were the state of consciousness measured with the Glasgow Coma Scale (GCS) of survivors at 14 days and Glasgow Outcome Scale Extended (GOSE) at 3 months.MethodsForty-nine patients with abbreviated injury scores of the head region ≥ 4 were included. Blood was sampled at 6, 12, 24 and 48 hours after injury. MMP-9 and c-Fn concentrations were measured by ELISA. The values of MMP-9 and c-Fn, and, for comparison, the value of the GCS on the field of the accident (fGCS), as predictors of the composite outcome of ICU LOS and death were assessed by logistic regression.ResultsThere was a linear relationship between maximal MMP-9 concentration, measured during the 6-12-hour period, and maximal c-Fn concentration, measured during the 24-48-hour period. The risk of staying longer than 9 days in the ICU or of dying was increased in patients with a maximal early MMP-9 concentration ≥ 21.6 ng/ml (OR = 5.0; 95% CI: 1.3 to 18.6; p = 0.02) or with a maximal late c-Fn concentration ≥ 7.7 μg/ml (OR = 5.4; 95% CI: 1.4 to 20.8; p = 0.01). A similar risk association was observed with fGCS ≤8 (OR, 4.4; 95% CI, 1.2-15.8; p = 0.02). No relationship was observed between MMP-9, c-Fn concentrations or fGCS and the GCS at 14 days of survivors and GOSE at 3 months.ConclusionsPlasma MMP-9 and c-Fn concentrations in the first 48 hours after injury are predictive for the composite endpoint of ICU LOS and death after severe TBI but not for consciousness at 14 days and outcome at 3 months.

Abstract 9069: Matrix Metalloproteinase-9 (MMP-9), Myeloperoxidase (MPO), And Soluble Cd40 Ligand (sCD40L) Levels in Patients with Non-calcified Coronary Artery Plaques Without Significant Stenosis by Coronary Computed Tomography Angiography (CCTA)

Objective: We aimed to evaluate whether matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), and soluble CD40 ligand (sCD40L) are elevated in patients with non-calcified plaques without significant coronary artery stenosis. These are the plaques that have been called “vulnerable” and may lead to acute coronary syndromes (ACS). Methods: We retrospectively analyzed all subjects who underwent coronary computed tomography angiography (CCTA) at our center between January 2009 and May 2010. All patients were referred for chest pain. After excluding patients who had calcified coronary plaques or significant coronary artery stenosis (stenosis&gt;50%), 174 patients were analyzed. Eighty-four patients who had non-calcified coronary plaques were enrolled in group A. Ninety patients who had no coronary plaque were enrolled in the normal control group (group B). The serum levels of MMP-9, MPO, and sCD40L were compared between the two groups. The relationship between these biomarkers and Framingham risk scores were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the ability of these biomarkers to predict the presence of non-calcified plaques. Results: A total of 128 non-calcified coronary plaques were found in 84 group A patients. The MMP-9 (641.33 ± 215.38 ng/ml vs 413.90 ± 182.01 ng/ml, p&lt;0.001) and MPO values (1073.69 ± 478.20 ng/ml vs 705.18 ± 289.68 ng /ml, p&lt;0.001) in group A were significantly higher than in group B. No significant difference was found in serum level of sCD40L between the two groups (8.65 ± 3.39 ng/ml vs 8.08 ± 4.00ng /ml, p=0.355). The Framingham risk score was significantly higher in group A than in group B (21 ± 5 vs 16 ± 4, p&lt;0.001). The serum levels of MMP-9 and MPO showed significant correlation with Framingham risk score (r = 0.799, p&lt;0.001; and r = 0.301, p&lt;0.001), but not for sCD40L (r=0.072, p=0.345). In terms of predicting non-calcified plaque, the areas under the ROC curves of MMP-9, MPO and sCD40L were 0.802 (95%CI = 0.735-0.868, p&lt;0.001), 0.738 (95%CI = 0.663-0.812, p&lt;0.001), and 0.575 (95%CI = 0.489-0.661, p=0.086), respectively. Conclusion: The serum levels of MMP-9 and MPO positively correlated with Framingham Risk Score and were significantly increased in patients with non-calcified plaque.

Matrix Metalloproteinase-9 for the Earliest Stage Acute Coronary Syndrome - Comparison With High-Sensitivity Troponin T -

Matrix metalloproteinase-9 (MMP-9) is regarded as a biomarker of plaque rupture or vulnerability and is elevated in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate the diagnostic value of MMP-9 for early ACS (≤4h of onset) and late ACS (>4h after onset), compared with high-sensitivity troponin T (hs-TnT). MMP-9 and hs-TnT were measured in 200 patients with ST elevation ACS (STEACS; 115 early STEACS and 85 late STEACS patients), and 66 patients with non-ST elevation ACS (NSTEACS; 25 early NSTEACS and 41 late NSTEACS patients). Forty patients with stable angina pectoris (SAP) were enrolled as a control group. MMP-9 levels were significantly higher in patients with early STEACS (P<0.001), early NSTEACS (P<0.001), late STEACS (P<0.001) and late NSTEACS (P=0.025) than SAP. MMP-9 levels were significantly higher in patients with early STEACS (P=0.017) and early NSTEACS (P=0.034) than late STEACS and late NSTEACS, respectively. Levels of hs-TnT were significantly lower in patients with early STEACS (P<0.001) and early NSTEACS (P=0.007) than late STEACS and late NSTEACS, respectively. On receiver operating characteristic curve analysis, area under the curve of early STEACS, early NSTEACS, late STEACS and late NSTEACS was 0.880, 0.782, 0.790 and 0.648 for MMP-9, and 0.707, 0.725, 0.993 and 0.920 for hs-TnT, respectively. MMP-9 levels were elevated earlier than hs-TnT and had a higher diagnostic value for early ACS, but not for late ACS, reflecting plaque rupture or vulnerability.

Changes in plasma content of matrix metallo proteinase-9 in acute cerebral infarction patients before and after thrombolytic therapy and its significance

To investigate the changes in the content of plasma matrix metallo proteinase-9 (MMP-9) in patients with acute cerebral infarction before and after thrombolytic therapy and its clinical significance. The levels of MMP-9 were determined in 34 patients with acute cerebral infarction before and after thrombolytic therapy, and 34 healthy individuals served as healthy control. Compared with the healthy controls, the levels of plasma MMP-9 before thrombolytic therapy were not significantly increased [(13.47±3.09) ng/L vs. (12.89±10.22) ng/L, P >0.05]. In contrast, MMP-9 values were significantly increased after thrombolytic therapy [(22.06±12.53) ng/L] compared with that in either before or healthy control group (both P<0.05). MMP-9 values were significantly higher in patients with hemorrhage after thrombolytic therapy (incidence rate was 26.5%, 9/34) compared with before treatment [(24.02±15.41) ng/L vs. (14.28±2.33) ng/L, P<0.05], and the values of MMP-9 were higher than those of patients without hemorrhage [(20.42±9.57) ng/L], but there was no statistically significant difference ( P >0.05). In patients with complete revascularization (revascularization rate was 58.8%, 20/34), MMP-9 level was markedly higher than before thrombolytic therapy after thrombolytic therapy [(19.26±7.94) ng/L vs. (13.63±3.02) ng/L, P<0.05], and the values of MMP-9 were higher than the no-revascularization patients [(18.97±4.23) ng/L], but there was no statistically significant difference ( P >0.05). Thrombolytic therapy activated MMP-9, and MMP-9 increased the risk of hemorrhage after thrombolytic therapy, and it participated in the mechanisms of hemorrhagic tendency after thrombolysis.

Adiposity and low‐grade systemic inflammation modulate matrix metalloproteinase‐9 levels in Greek children with sleep apnea

Matrix metalloproteinase-9 (MMP-9) plasma levels correlate with C-reactive protein (CRP) concentrations and they are both increased in adults with obstructive sleep apnea (OSA). No studies have evaluated MMP-9 levels in children with sleep apnea and CRP is not consistently elevated in pediatric OSA. The aim of this investigation was to evaluate the association of severity of OSA, adiposity, and CRP with MMP-9 plasma levels in Greek children. Consecutive children with snoring who underwent polysomnography and were found to have OSA (obstructive apnea-hypopnea index-OAHI > or = 1 episode/hr) were recruited. Subjects without OSA (OAHI < 1 episode/hr) were included for comparison. Morning plasma MMP-9 and CRP were measured. Twenty-nine children with moderate-to-severe OSA (age 5.4 +/- 1.5 years; OAHI 13.9 +/- 13.0 episodes/hr), 55 participants with mild OSA (6.4 +/- 2.6 years; OAHI 2.4 +/- 1.1 episodes/hr) and 22 subjects without OSA (6.8 +/- 2.6 years; OAHI 0.6 +/- 0.2 episodes/hr) were studied. Children with moderate-to-severe OSA were similar to those with mild OSA or without OSA regarding ln-transformed MMP-9 values (5.87 +/- 0.60 vs. 5.84 +/- 0.55 vs. 5.80 +/- 0.46; P > 0.05) and CRP concentrations (0.22 +/- 0.29 mg/dl vs. 0.21 +/- 0.36 vs. 0.13 +/- 0.16 mg/dl; P > 0.05). In multiple linear regression, body mass index (P = 0.027) and CRP levels (P = 0.008), but not OAHI or SpO(2) nadir (P > 0.05), were significantly related to MMP-9 values. Adiposity and systemic inflammation unrelated to OSA severity, modulate MMP-9 levels in Greek children.