Plasma Matrix Metalloproteinase-9 Concentrations Research Articles

Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment response and white matter density deficits

Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

Abstract TP155: Predictive Value of Plasma Matrix Metalloproteinase-9 Concentrations for Hemorrhagic Transformation in Acute Ischemic Stroke: A Systematic Review and Diagnostic Accuracy Meta-Analysis

Background: Hemorrhagic transformation (HT) is a critical sequela of acute ischemic stroke (AIS). Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathophysiology of hemorrhagic transformation (HT) post-acute ischemic stroke (AIS). However, the diagnostic accuracy of plasma MMP-9 concentrations as a predictive marker for HT remains inconsistent across studies. Aim: This study aims to determine the potential of plasma MMP-9 concentrations as an indicator for HT in AIS patients. Methods: Systematic reviews of leading databases such as PubMed, Embase, and the Cochrane Library were performed until March 2023. Studies were included assessing the diagnostic accuracy of plasma MMP-9 concentrations in predicting HT after AIS. Statistical analyses were conducted using R software (version 4.0.3) and the mada package. This analytical method enabled the pooling of sensitivity, specificity, false-positive rates, diagnostic odds ratio, as well, as both positive and negative Likelihood Ratios. Outcomes are reported within a 95% Confidence Interval (CI). Results: Our analysis included 4 studies with a total of 378 patients, of whom 79 developed hemorrhagic transformation. Plasma MMP-9 displayed notable predictive capabilities with a pooled sensitivity of 92.4% (95% CI: 77-97.8%, I 2 =0%), highlighting its proficiency in detecting HT cases. Its specificity was 78.3% (95% CI: 73.2-82.6%, I 2 =0%), emphasizing its accuracy in distinguishing non-HT cases. However, there was a false-positive rate of 21.7% (95% CI: 17.4-26.8%). The positive Likelihood Ratio was 4.25 (95% CI: 3.36-5.38), and the notably low negative Likelihood Ratio was 0.09 (95% CI: 0.03-0.32). The diagnostic odds ratio, suggesting strong discriminative power, was 43.72 (95% CI: 11.73-162.91). Conclusion: Our analysis underscores the promising role of plasma matrix metalloproteinase-9 concentrations in predicting hemorrhagic transformation following an acute ischemic stroke. However, the broad adoption in clinical settings mandates further confirmatory studies and validation across heterogeneous populations.

Effect of spironolactone therapy on the activity of the matrix metalloproteinase system in patients with heart failure after COVID-19

Aim. To assess the change in the activity of the matrix metalloproteinase (MMP) system after 6-month spironolactone therapy in patients with heart failure (HF) with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF) after coronavirus disease 2019 (COVID-19).Material and methods. The study included 90 patients treated at the University Clinical Hospital № 4 of the I.M. Sechenov First Moscow State Medical University with a laboratory-confirmed COVID-19. There were following inclusion criteria: age of 18-85 years; the presence of HFpEF and HFmrEF. The patients were randomized into two groups: group I (n=60) — patients with 6-month spironolactone therapy (25 mg/day) in addition to the standard therapy for HF, spironolactone was taken at a dose of 25 mg/day; Group II (comparison group, n=30) — patients who received standard therapy without spironolactone. All patients were determined plasma MMP concentrations.Results. There were no significant differences in the levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) between the groups when included in the study. A repeated investigation revealed a significant decrease in the concentrations of MMP-9 and TIMP-1 only in group I. In patients of group II, there were no significant changes in the plasma concentrations of MMP-9 and TIMP-1. The MMP-9/TIMP-1 ratio during the initial examination of patients did not have significant differences. After 6-months therapy, a significant decrease in the ratio of MMP-9/TIMP-1 was observed only in patients taking spironolactone.Conclusion. The results obtained confirm a significant decrease in MMP system activity after 6-month spironolactone therapy in patients with HFpEF and HFmrEF after COVID-19. The described antifibrotic effects of spironolactone make it possible to recommend the use of this drug in this category of patients to reduce the negative effect of MMPs on cardiovascular system.

Relevance of Plasma Matrix Metalloproteinase-9 for Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Cell Transplantation

Bronchiolitis obliterans syndrome (BOS) is a highly morbid form of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Several plasma proteins have been identified as biomarkers for BOS after lung transplantation. The relevance of these biomarkers in BOS patients after allogeneic HCT has not been examined. We hypothesized that biomarkers associated with BOS after lung transplantation are also associated with BOS after allogeneic HCT. We tested plasma samples from 33 adult HCT patients who participated in a phase II multicenter study of fluticasone, azithromycin, and montelukast (FAM) treatment for new-onset BOS (NCT01307462), and matched control samples of HCT patients who had non-BOS chronic GVHD (n=31) and those who never experienced chronic GVHD (n=29) (NCT00637689 and NCT01902576). Candidate biomarkers included matrix metalloproteinase-9 (MMP-9), MMP-3, and chitinase-3-like-1 glycoprotein (YKL-40). MMP-9 concentrations were higher in the patients with BOS compared with those with non-BOS chronic GVHD (P=.04) or no chronic GVHD (P < .001). MMP-3 concentrations were higher in patients with BOS (P < .001) or non-BOS chronic GVHD (P < .001) compared with those with no chronic GVHD. YKL-40 concentrations did not differ statistically among the 3 groups. MMP-9 concentrations before starting FAM therapy were higher in patients who experienced treatment failure within 6 months compared with those with treatment success (P=.006), whereas MMP-3 or YKL-40 concentrations did not differ statistically between these 2 groups. Patients with an MMP-9 concentration ≥200,000 pg/mL before starting FAM therapy had worse overall survival compared with those with lower MMP-9 concentrations. Our data suggest that plasma MMP-9 concentration could serve as a relevant biomarker at diagnosis of BOS after allogeneic HCT for prognostication of survival and for prediction of treatment response. Further validation is needed to confirm our findings.

Evaluation of matrix metalloproteinase-9 plasma levels in untreated new Relapsing-remitting multiple sclerosis patients and their first-degree family.

Matrix metalloproteinase, especially Matrix metalloproteinase-9 (MMP-9) has vital roles in the disruption of blood barrier, neuroinflammation and pathogenesis of multiple sclerosis (MS) patients.The goal of this study is to estimate the plasma levels of MMP-9 in the first-degree family of MS patients.35 untreated patients with definite RRMS (Relapsing-Remitting Multiple sclerosis) according to the McDonald criteria, 24 healthy controls (HC) and 26 high-risk families of untreated RRMS patients were enrolled in the study. Plasma levels of MMP-9 were analyzed by ELISA (enzyme-linked immunosorbent assay).Although the plasma protein levels of MMP-9 were elevated significantly in the untreated RRMS group (P < 0.05, P = 0.0203) as compared to the control group, but the family of MS patients was not significance (P = 0.208). The mean plasma MMP-9 concentration for HC, untreated RRMS and high-risk group was 322.268pg/ml, 611.926pg/ml and 518.939pg/ml respectively.MMP-9 was used to understand the role of this biomarker in the pathogenesis of MS in the high-risk group. It found that plasma levels of MMP-9 in the new cases of MS were increased considerably. Confirming the importance of MMP-9 as a predictive marker in the high-risk group will be needed more researches.

Increased serum level of high sensitivity troponin T even prior to surgery can predict adverse events during carotid endarterectomy.

Perioperative stress affects the outcome of carotid endarterectomy performed under regional anesthesia. Here we aimed to explore the temporal profile of the stress marker cortisol and its relationship to high-sensitivity troponin-T, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and S100B as an indicator of blood-brain barrier alteration in the systemic circulation. Prospective part of the study: a total of 31 patients with significant carotid stenosis scheduled for carotid endarterectomy in regional anesthesia were enrolled. Follow-up part of the study and retrospective analysis of the outcome: each patient was followed up to five years and morbidity as well as mortality data were collected from an electronic database. Blood samples from each patient were serially taken; prior to surgery (T1), at the time of reperfusion (T2), 24 h (T3) and 72 h later postoperatively (T4), then the plasma concentration of each biomarker was measured. Besides, the clinical and surgical factors and perioperative adverse events were recorded. More positive correlations were found between: the early change of S100B (T2-T1) and late change in plasma cortisol level (T4-T3) (r = 0.403; p < 0.05); the early change of cortisol (T2-T1) and the early postoperative change of plasma matrix metalloproteinase-9 level (T3-T2) (r = 0.432; p = 0.01); the plasma concentration of tissue inhibitor of metalloproteinase-1 at 24 postoperative hours and the late change in plasma high-sensitivity troponin-T level (T4-T3) (r = 0.705; p < 0.001). Five patients needed an intraoperative shunt in whom the high-sensitivity troponin-T was elevated even prior to surgery, but definitive stroke never occurred. Plasma matrix metalloproteinase-9 concentration at reperfusion independently predicted the five-year mortality with a cut-off value of 456 ng/ml (sensitivity: 86%, specificity: 84%, area 0.887, p = 0.002). A higher intraoperative change in S100B level reflecting carotid endarterectomy induced acute silent brain ischemia was associated with more pronounced post-operative change of cortisol. An early elevation of cortisol was found to be associated with a delayed increase of matrix metalloproteinase-9. Importantly, an increased high-sensitivity troponin-T even prior to carotid endarterectomy may predict clamp intolerance, and elevated matrix metalloproteinase-9 at reperfusion suggests a poor outcome.

Effects of ultrasound-guided paravertebral block on MMP-9 and postoperative pain in patients undergoing VATS lobectomy: a randomized, controlled clinical trial

BackgroundLocal anesthesia can reduce the response to surgical stress and decrease the consumption of opioids, which may reduce immunosuppression and potentially delay postoperative tumor recurrence. We compared paravertebral block (PVB) combined with general anesthesia (GA) and general anesthesia regarding their effects on postoperative pain and matrix metalloproteinase-9 (MMP-9) after video-assisted thoracoscopic surgery (VATS) lobectomy.Methods54 patients undergoing elective VATS lobectomy at a single tertiary care, teaching hospital located in Qingdao between May 2, 2018 and Sep 28, 2018 were randomised by computer to either paravertebral block combined with general anesthesia or general anesthesia. The primary outcomes were pain scores at rest and on cough at 1, 4, 24, and 48 h after surgery. The secondary outcome were plasma concentrations of MMP-9, complications, and length of postoperative hospital stay.Results75 were enrolled to the study, of whom 21 were excluded before surgery. We analyzed lobectomy patients undergoing paravertebral block combined with general anesthesia (n = 25) or general anesthesia (n = 24). Both groups were similar regarding baseline characteristics. Pain scores at rest at 4 h and 24 h, on cough at 4 h were lower in PVB/GA group, compared with GA group (P < 0.05). There were no difference in pain scores at rest at 1 h, 48 h and on cough at 1 h, 24 h, and 48 h between groups. Patients in the PVB/GA group showed a greater decrease in plasma MMP-9 level at T1 and T2 after VATS lobectomy (P < 0.05). Postoperative complications and length of stay did not differ by anesthetic technique.ConclusionsThe paravertebral block/general anesthesia can provide statistically better pain relief and attenuate MMP-9 response to surgery and after VATS lobectomy. This technique may be beneficial for patients to recover rapidly after lung surgery and reduce postoperative tumor recurrence.Trial registrationChinese Clinical Trial registration number ChiCTR1800016379. Registered 28 May 2018.

Predictive value of plasma matrix metalloproteinase-9 concentrations for spontaneous haemorrhagic transformation in patients with acute ischaemic stroke: A cohort study in Chinese patients

Whether matrix metalloproteinase 9 (MMP-9) concentrations in plasma predict risk of spontaneous haemorrhagic transformation (sHT) in acute ischaemic stroke is unclear. From 1 March 2003 to 27 February 2006, patients with acute ischaemic stroke admitted to West China Hospital within 24 h of onset and healthy controls were enrolled and blood samples obtained. Plasma MMP-9 concentrations were determined using enzyme-linked immunosorbent assay, and sHT was diagnosed based on brain computed tomography or magnetic resonance performed 3–14 d after stroke onset. MMP-9 concentrations were compared for sHT patients, non-sHT patients and healthy controls. The threshold concentration for predicting sHT was determined using receiver operating characteristic analysis and the association between MMP-9 concentration and sHT was tested. One hundred and sixty-eight stroke patients and 40 healthy controls were included. Spontaneous HT occurred in 17.3% (29/168) of stroke patients and median plasma MMP-9 concentration in the sHT subgroup [244.3 ng/mL; interquartile range (IQR), 190.6–431.4] was significantly higher than in the non-sHT subgroup (110.0 ng/mL; IQR, 54.4–172.2) as well as in healthy controls (63.3 ng/mL; IQR 37.9–84.9) (both P < 0.001). We identified 181.7 ng/mL as the threshold MMP-9 concentration, for which the positive predictive value was 48% and the negative predictive value was 96%. After controlling for potential confounding factors, MMP-9 concentration >181.7 ng/mL was an independent predictor of sHT (odds ratio 18.8, 95% confidence interval 6.0–58.5, P < 0.001). Plasma MMP-9 concentration >181.7 ng/mL within 24 h after stroke onset independently predicts sHT in patients with ischaemic stroke.

The platelet phenotype in patients with ST-segment elevation myocardial infarction is different from non–ST-segment elevation myocardial infarction

It is assumed that platelets in diseased conditions share similar properties to platelets in healthy conditions, although this has never been examined in detail for myocardial infarction (MI). We examined platelets from patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) compared with platelets from healthy volunteers to evaluate for differences in platelet phenotype and function. Platelet activation was examined and postreceptor signal transduction pathways were assessed. Platelet-derived plasma biomarkers were evaluated by receiver operator characteristic curve analysis. Maximum platelet activation through the thromboxane receptor was greater in STEMI than in NSTEMI but less through protease-activated receptor 1. Extracellular-signal related-kinase 5 activation, which can activate platelets, was increased in platelets from subjects with STEMI and especially in platelets from patients with NSTEMI. Matrix metalloproteinase 9 (MMP9) protein content and enzymatic activity were several-fold greater in platelets with MI than in control. Mean plasma MMP9 concentration in patients with MI distinguished between STEMI and NSTEMI (area under curve [AUC] 75% [confidence interval (CI) 60-91], P = 0.006) which was superior to troponin T (AUC 66% [CI 48-85, P = 0.08), predicting STEMI with 80% sensitivity (95% CI 56-94), 90% specificity (CI 68-99), 70% AUC (CI 54-86, P < 0.0001), and NSTEMI with 50% sensitivity (CI 27-70), 90% specificity (CI 68-99), 70% AUC (CI 54-86, P = 0.03). Platelets from patients with STEMI and NSTEMI show differences in platelet surface receptor activation and postreceptor signal transduction, suggesting the healthy platelet phenotype in which antiplatelet agents are often evaluated in preclinical studies is different from platelets in patients with MI.

C-1562T polymorphism of matrix metalloproteinase-9 (MMP-9) gene associated with elevated level of plasma MMP-9 concentration in patient with acute myocardial infarction (AMI) in Denpasar-Bali

C-1562T polymorphism of matrix metalloproteinase-9 (MMP-9) gene associated with elevated level of plasma MMP-9 concentration in patient with acute myocardial infarction (AMI) in Denpasar-Bali

Plasma matrix metalloproteinase-9 levels predict intensive care unit mortality early after severe traumatic brain injury

ABSTRACTObjectives: Matrix metalloproteinase-9 (MMP-9) is an inducible metalloproteinase that can degrade the cerebrovascular matrix leading to disruption of the blood–brain barrier and exacerbation of oedema in neurotrauma. Therefore, our aim was to determine whether MMP-9 plasma levels were associated with intensive care unit (ICU) mortality after severe traumatic brain injury (TBI) despite the presence of extracerebral injuries.Methods: This cohort enrolled 80 patients who suffered severe TBI (Glasgow Coma Scale: 3–8 at hospital admission). The plasma MMP-9 level was determined by enzyme-linked immunosorbent assay assay at ICU admission.Results: Severe TBI was associated with a 32.5% ICU mortality rate. There was no association between the presence of extracerebral injuries (72.5% of the patients) and ICU mortality (P = 0.419). Higher plasma MMP-9 concentrations were associated with fatal outcome: 181.1 ± 16.0 ng/mL for survivors and 257.0 ± 23.2 ng/mL for nonsurvivors (mean ± S.E.M., P = 0.009). In contrast, there was no significant difference between MMP-9 levels and associated lesions: 220.8 ± 26.3 ng/mL for isolated TBI and 196.8 ± 15.8 ng/mL for patients with extracerebral injuries (P = 0.397).Conclusion: Increased plasma MMP-9 levels predicted short-term fatal outcome following severe TBI, regardless the presence of extracerebral injuries.

The plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 are elevated in patients with endometriosis.

Enzyme matrix metalloproteinase-9 is a member of the matrix metalloproteinase family, which is critical to normal tissue remodelling during embryogenesis and wound healing. In patients with endometriosis, increased expression and activity of matrix metalloproteinase-9 have been observed in ectopic endometrium, but the plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 in patients with endometriosis and their relation to disease severity have not been clear. The aim of the study was to investigate the concentrations of matrix metalloproteinase-9 in plasma and peritoneal fluid of patients with endometriosis. A prospective case-control study was conducted in Jinan Military General Hospital between January 2010 and December 2013. Fifty patients with proven endometriosis and 26 endometriosis-free controls were enrolled in this study. Patients with endometriosis were evaluated and divided into moderate/severe endometriosis group (stage I-II, n = 26) and minimal/mild endometriosis group (stage III-IV, n = 24) according to the revised criteria of the American Society for Reproductive Medicine. Blood samples and peritoneal fluid were obtained from both patients and controls. Matrix metalloproteinase-9 was measured using enzyme-linked immunosorbent assay in plasma and peritoneal fluid. The concentration of matrix metalloproteinase-9 between different groups was compared and its correlation to disease severity was analysed. Plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 in patients with endometriosis were higher than that in controls. In addition, those patients with moderate/severe endometriosis had significantly higher plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 compared to those with minimal/mild endometriosis. Matrix metalloproteinase-9 concentrations in plasma and peritoneal fluid were both positively correlated with severity of endometriosis and plasma matrix metalloproteinase-9 concentrations had a positive correlation with peritoneal fluid matrix metalloproteinase-9 concentrations in patients with endometriosis. Increased concentrations of plasma and peritoneal fluid concentrations of matrix metalloproteinase-9 appear to be associated with disease severity of endometriosis and may serve as an alternative biomarker to determine disease severity of endometriosis.

The association between plasma matrix metalloproteinase-9 concentration and endoleak after endovascular aortic aneurysm repair: A meta-analysis

BackgroundThe most common complication after endovascular aneurysm repair (EVAR) is continued perfusion of the aneurysmal sac, known as endoleak. Assessment of markers released from the aneurysm wall into the circulation has been suggested as a possible alternative for detecting endoleaks. The aim of this meta-analysis was to examine if circulating concentrations of matrix metalloproteinase (MMP)-9 were higher in patients with endoleak after EVAR. MethodsA systematic search of the MEDLINE, EMBASE, Scopus, Web of Science and Cochrane Library Databases was conducted. Studies reporting circulating MMP-9 concentrations in patients who did and did not have endoleaks after EVAR that met inclusion and exclusion criteria were included. A meta-analysis using a random effects model was performed to assess the association between circulating concentrations of MMP-9 and endoleak. Sensitivity analyses were performed using the one-study remove approach. Study quality was assessed using a quality assessment tool. ResultsPrior to EVAR, plasma concentrations of MMP-9 were similar in patients that did and did not subsequently develop an endoleak (Standardised mean difference: −0.13; 95% confidence interval, −0.63 to 0.37, p=0.60). 1 month after EVAR, plasma concentrations of MMP-9 were non-significantly higher in patients that had an endoleak (Standardized mean difference: 0.56; 95% CI −0.02 to 1.15, p=0.06). 3 months after EVAR, plasma concentrations of MMP-9 were higher in patients that had an endoleak (Standardised mean difference: 1.42; 95% confidence interval, 0.48–2.36, p<0.003). ConclusionsThis meta-analysis suggests that plasma MMP-9 concentrations measured 3 months after EVAR are higher in patients that have an endoleak. It remains to be established whether plasma MMP-9 testing is sufficiently accurate for use as a surveillance test for endoleak after EVAR.

Blood pressure control predicts plasma matrix metalloproteinase-9 in diabetes mellitus type II.

IntroductionMatrix metalloproteinase-9 (MMP-9) plays an important role in extracellular and vascular remodelling. We aimed therefore to assess the role of blood pressure (BP) control on plasma MMP-9 in relation to the presence of diabetes mellitus (DM) type II.Material and methodsPlasma MMP-9 was measured in 61 patients who were divided into two groups depending on their BP control as follows: 49 patients with uncontrolled arterial hypertension (AH) defined as BP values > 130/80 mm Hg and 12 patients with optimal blood pressure values. Plasma MMP-9 levels were measured with immunoassay at discharge. Group comparisons were made with the independent t-test, Mann-Whitney U-test and χ2 test where appropriate. The associations of the variables with MMP-9 were investigated with linear regression analyses.ResultsThe diabetics made up 34.4% of the investigated patients. Frequency of DM did not differ between the two BP groups (30.0% vs. 36.6%, p > 0.05). Plasma MMP-9 concentrations differed significantly between the diabetics vs. non-diabetics (median: 1.9 ng/ml, range: 1.0–7.3 vs. 1.4 ng/ml, range: 0.5–4.7, p < 0.05). Stratification across the categories of BP control showed a significant correlation between plasma MMP-9 and DM type II only in the uncontrolled BP group. The significance of that relationship disappeared in the group of patients with optimal BP control.ConclusionsPlasma values of MMP-9 are raised in patients with DM type II. The results revealed the impact of the combination of uncontrolled AH and DM type II on vascular remodelling processes.

Proteomic and genomic analyses suggest the association of apolipoprotein C1 with abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is an important cause of mortality in the elderly. Mouse models are widely used to investigate AAA pathogenesis but their suitability for biomarker discovery is unexplored. We conducted a three-phase study. Phase 1: Aortas from angiotensin-II-infused apolipoprotein E deficient (ApoE(-/-) ) mice with and without AAA were assessed via iTRAQ and analyzed in silico to identify potential circulating markers. Microarray data from ApoE(-/-) mice and human patients were analyzed in parallel. Phase 2: Putative markers were compared between datasets to shortlist common candidates. Phase 3: The relationship of two shortlisted markers and AAA presence was assessed. iTRAQ identified eight proteins with biomarker potential. Microarray data identified 72 and 96 potential biomarkers from ApoE(-/-) mice and human patients, respectively. All three datasets suggested apolipoprotein C1 (ApoC1) as a marker for AAA; microarray data identified matrix metalloproteinase 9 (MMP9) as a second potential marker. Plasma ApoC1 and MMP9 concentrations positively correlated with AAA diameter in ApoE(-/-) mice. ApoC1 may be a novel biomarker for AAA.

Effects of atorvastatin on plasma matrix metalloproteinase-9 concentration after glial tumor resection; a randomized, double blind, placebo controlled trial

BackgroundNeurosurgical procedures such as craniotomy and brain tumor resection could potentially lead to unavoidable cerebral injuries. Matrix metalloproteinase-9 (MMP-9) is up-regulated in neurological injuries. Statins have been suggested to reduce MMP- 9 level and lead to neuroprotection. Atorvastatin preoperatively administered to evaluate its neuroprotective effects and outcome assessment in neurosurgical-induced brain injuries after glial tumor resection. In this prospective, randomized, double-blind, placebo-controlled trial, 42 patients undergoing glial tumor surgery randomly received 40 mg atorvastatin or placebo twice daily from seven days prior to operation and continued for a 3 weeks period. Plasma MMP-9 concentration measured 4 times, immediately before starting atorvastatin or placebo, immediately before surgery, 24 hours and two weeks after the surgery. Karnofsky performance score was assessed before first dose of atorvastatin as a baseline and 2 months after the surgery.ResultsKarnofsky performance scale after surgery raised significantly more in Atorvastatin group (11.43 +/- 10.62 vs. 4.00 +/- 8.21) (p = 0.03). Atorvastatin did not significantly reduce MMP-9 plasma concentration 24 hours after surgery in comparison to placebo. No statistical significance detected regarding length of hospital stay among the groups. Significant reduction in MMP-9 plasma concentration was recorded in atorvastatin group two weeks after surgery (p = 0.048).ConclusionsSignificant statistical differences detected with atorvastatin group regarding MMP-9 plasma concentration, clinical outcome and Karnofsky performance score. Consequently, atorvastatin use may lead to better outcome after neurosurgical procedures.

Noninvasive Perioperative Evaluation of Right Ventricular Function in Children With Tetralogy of Fallot

Early and accurate noninvasive means of identifying right ventricular (RV) dysfunction in children with tetralogy of Fallot (TOF) are needed. RV function was examined using tissue Doppler imaging (TDI), strain rate (SR), and strain analysis (SA) in children before (N = 37) and after (6-12 months; N = 32) TOF repair, and in a control group of children (N = 37). Plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and matrix metalloproteinase 9 (MMP-9) were measured. TDI, SR, and SA revealed that RV systolic and diastolic function indices were lower preoperatively in the TOF group compared with the control group, and did not improve after TOF repair. Plasma NT-proBNP concentrations were significantly higher in the TOF group pre- and postoperatively compared with the control group. In the preoperative TOF group, NT-proBNP concentration was significantly correlated with peak systolic SR and systolic strain in the mid segments of RV free wall. Plasma MMP-9 concentrations were significantly increased in the preoperative TOF group compared with the control group, and significantly correlated with plasma NT-proBNP and logNT-proBNP concentrations. RV function correlated with plasma NT-proBNP concentrations in children with TOF. Assessment of this noninvasive measure may help identify RV dysfunction in patients with TOF before they become clinically symptomatic.

The circulating level of MMP-9 and its ratio to TIMP-1 as a predictor of severity in patients with community-acquired pneumonia

BackgroundHere, we have examined the plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), the MMP-9/TIMP-1 molar ratio, the TIMP-1 single nucleotide polymorphisms (SNPs) 372C/T and the susceptibility to community-acquired pneumonia (CAP). MethodsAn enzyme-linked immunosorbent assay (ELISA) was used to measure plasma MMP-9 and TIMP-1 concentrations in 60 patients with CAP and 60 healthy individuals. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to detect the TIMP-1 SNPs 372C/T. ResultsThe plasma MMP-9, TIMP-1 levels and the MMP-9/TIMP-1 molar ratio were significantly increased in patients with CAP compared to normal controls. The MMP-9/TIMP-1 molar ratio decreased significantly in patients with CAP after treatment. Furthermore, the plasma TIMP-1 concentration was positively correlated with the pneumonia severity index (PSI), the CURB score, the results of the acute physiology and chronic health evaluation II (APACHE II) and the length of the hospital stay. No significant difference was found in the genotype distribution of TIMP-1 372C/T between patients with CAP and normal controls. ConclusionsWe hypothesize that MMP-9 levels and the MMP-9/TIMP-1 molar ratio play a role in the development of CAP and are related to the severity of CAP. Based on our data, we suggest that incorporating plasma MMP-9 levels and the MMP-9/TIMP-1 molar ratio into a clinical evaluation will aid in CAP diagnosis.

Peripheral Blood Levels of Matrix and Inflammatory Mediators are Elevated in Tunisian Patients with Acute Coronary Syndromes

The aim of the present study was to investigate differences of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in the peripheral blood of patients admitted with acute coronary syndrome (ACS), in correlation with the widely accepted markers of inflammatory activity, C-reactive protein, fibrinogen, and white blood cell number. 315 patients with ACS (165 unstable angina pectoris/non-ST-elevation myocardial infarction, 150 ST-elevation myocardial infarction), 111 stable angina (SA) patients, and 296 control subjects were enrolled in the study. All biochemical analyses were carried out using a Hitachi 912 analyzer (Roche). Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined in citrate plasma by ELISA methods. White blood cells (WBC) and fibrinogen were also determined. The plasma concentrations of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, C-reactive protein, fibrinogen, and white blood cells in patients with acute coronary syndrome were significantly elevated compared to the control group (p < 0.001). MMP-9/TIMP-1 ratio was significantly higher in SA and ACS patients (p < 0.001) than controls. Strong positive associations were observed between MMP-9 and TIMP-1 (r = 0.213, p < 0.01), MMP-9 and CRP (r = 0.103, p < 0.01), MMP-9 and fibrinogen (r = 0.299, p < 0.01), MMP-9 and WBC (r = 0.135, p < 0.01), TIMP-1 and CRP (r = 0.219, p < 0.01), TIMP-1 and Fibrinogen (r = 0.226, p < 0.01), TIMP-1 and WBC (r = 0.094, p < 0.1), CRP and fibrinogen (r = 0.158, p < 0.01), CRP and WBC (r = 0.156, p < 0.01, and finally between fibrinogen and WBC (r = 0.234, p < 0.01) in the patients with ACS. In conclusion, our observations suggest that ACS shows an increase in both remodeling and inflammation markers. In addition, the strong relationship with MMP-9 and inflammatory mediators such as CRP, fibrinogen, and WBC in ACS patients suggests that MMP-9 might be an additional marker and/or consequence of inflammatory components in ACS.

Matrix Metalloproteinase‐2 and ‐9 Levels in Patients with Dilated Ascending Aorta and Bicuspid Aortic Valve

Predictors of aortic dilatation are not well-described in patients with bicuspid aortic valve (BAV). Changes in extracellular matrix composition in the aortic wall may play an important role. Our study aimed to examine the relationship between ascending aortic dilatation and biochemical markers for collagen metabolism, such as matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) levels in patients with BAV. All patients underwent cardiac echocardiography using a standard protocol, and aortic measurements were made in end-diastole. One hundred twelve BAV patients with no or mild valvular impairment were recruited and grouped according to the aortic dimensions corrected for body surface area (BSA) and age. There were 54 patients with dilated ascending aorta (Group 1) and 58 patients with nondilated ascending aorta (group 2). The plasma levels of MMP-2 and MMP-9 were determined by ELISA. The mean ascending aorta diameter was 4.49 ± 0.49 mm in group 1 and 3.51 ± 0.46 mm in group 2 (P < 0.001). There were no significant difference in gender, BSA, presence of hypertension, diabetes mellitus, hyperlipidemia, and smoking between the 2 groups. Nevertheless, no significant difference was observed in the levels of MMP-2 and MMP-9 between the 2 groups. The ascending aorta diameter correlated significantly with age (r = 0.438 P < 0.001). No significant correlation was observed between plasma MMP-2 and MMP-9 concentration and ascending aorta diameter, respectively (r = -0.005 P = 0.58, r = -0.106 P = 0.07). Multivariate analysis showed that age was independent predictor of aortic dilatation (P ≤ 0.001). Age was an independent predictor of aortic dilatation in patients with BAV, whereas MMP-2 and 9 levels were not relevant by aortic dilatation.