Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with diabetic nephropathy have a high rate of cardiovascular events and mortality. Nontraditional cardiovascular risk factors such as oxidative stress and inflammation are thought to be particularly important in mediating these events. Studies suggest that thiazolidinediones (TZDs) can reduce the level of nontraditional cardiovascular risk in people with or without diabetes mellitus. Whether this benefit occurs in patients with diabetic nephropathy is unknown. I hypothesized that the TZD pioglitazone will mitigate oxidative stress and inflammation compared with glipizide in patients with overt diabetic nephropathy. Markers of oxidative stress (plasma and urine albumin carbonyl and total protein carbonyls and malondialdehyde), inflammation [white blood cell (WBC) count, C-reactive protein (CRP), plasma IL-6, TNF-alpha], and plaque stability [matrix metalloproteinase 9 (MMP-9)] were measured in frozen samples obtained from patients with overt diabetic nephropathy participating in a randomized, open-label, blinded end-point, 16-wk trial with glipizide (n = 22) or pioglitazone (n = 22). Pioglitazone therapy in men with advanced diabetic nephropathy reduced WBC count by 1,125/mul (P < 0.001), CRP by 41% (P = 0.042), IL-6 by 38% (P = 0.009), and MMP-9 by 29% (P = 0.016). Specific differential reductions in WBC count of 1,251/mul (P = 0.009) and reduction in IL-6 of 58% with pioglitazone (P = 0.001) were seen compared with glipizide. There were no statistically significant changes observed with plasma TNF-alpha concentrations or markers of oxidative stress with either hypoglycemic agent. In conclusion, pioglitazone reduces proinflammatory markers in patients with overt diabetic nephropathy, which indicates potentially beneficial effects on overall cardiovascular risk. This surrogate end point needs to be confirmed in trials designed to demonstrate cardiovascular protection.
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PMID:Anti-inflammatory effects of short-term pioglitazone therapy in men with advanced diabetic nephropathy. 1615 95

Previous studies have shown that matrix metalloproteinase 9 (MMP-9) degrades basement membrane components in inflammation, but the change of serum MMP-9 level in the progression of acute pancreatitis remains unclear. The aim of our study was to assess the value of MMP-9 as a prognostic marker in acute pancreatitis. The prospective study included 10 patients with severe acute pancreatitis (SAP) and 10 patients with mild acute pancreatitis. The study also enrolled 10 healthy individuals as control. The serum MMP-9 level, serum C-reactive protein (CRP) level, serum tumor necrosis factor alpha (TNF-alpha) level and acute physiology and chronic health evaluation (APACHE) II score were measured at 1 hr and 48 hrs after admission. APACHEII scores and serum MMP-9, TNF-alpha and CRP levels were significantly increased in patients with SAP compared to those with mild acute pancreatitis and control subjects at 1 hr after admission (p < 0.01). When the states of illness were improved, the levels of the above-mentioned markers were decreased in patients with SAP at 48 hrs after admission (1 hr vs 48 hrs, p < 0.01 or p < 0.05). Furthermore, significant positive correlation was found between serum MMP-9 level and serum TNF-alpha level, serum CRP level or APACHEII score in patients at 1 hr after admission (MMP-9/TNF-alpha, r = 0.956; MMP-9/CRP, r = 0.935; MMP-9/APACHE II score, r = 0.957; p < 0.01). These results suggest that MMP-9 is involved in the deterioration of SAP and serum MMP-9 level is a valuable assessment marker for the severity of SAP.
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PMID:Serum matrix metalloproteinase 9 as a marker for the assessment of severe acute pancreatitis. 1649 35

Recent investigations of atherosclerosis have focused on inflammation, providing new insight into mechanisms of disease. Inflammatory cytokines involved in vascular inflammation stimulate the generation of endothelial adhesion molecules, proteases, and other mediators, which may enter the circulation in soluble form. These primary cytokines also induce production of the messenger cytokine interleukin-6, which stimulates the liver to increase production of acute-phase reactants such as C-reactive protein. In addition, platelets and adipose tissue can generate inflammatory mediators relevant to atherothrombosis. Despite the irreplaceable utility of plasma lipid profiles in assessment of atherosclerotic risk, these profiles provide an incomplete picture. Indeed, many cardiovascular events occur in individuals with plasma cholesterol concentrations below the National Cholesterol Education Program thresholds of 200 mg/dL for total cholesterol and 130 mg/dL for low-density lipoprotein (LDL) cholesterol. The concept of the involvement of inflammation in atherosclerosis has spurred the discovery and adoption of inflammatory biomarkers for cardiovascular risk prediction. C-reactive protein is currently the best validated inflammatory biomarker; in addition, soluble CD40 ligand, adiponectin, interleukin 18, and matrix metalloproteinase 9 may provide additional information for cardiovascular risk stratification and prediction. This review retraces the biology of atherothrombosis and the evidence supporting the role of inflammatory biomarkers in predicting primary cardiovascular events in this biologic context.
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PMID:Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. 1816 Jul 25

Type 2 diabetes mellitus is associated with elevated plasma triglyceride levels, low high-density lipoprotein cholesterol, and a high incidence of cardiovascular disease. Hydroxymethylglutaryl-coenzyme A reductase inhibitors and fibrates are frequently used in the treatment of diabetic dyslipidemia, but their specific impact on the inflammation processes involved in atherosclerosis remains to be fully characterized. The objective of this 2-group parallel study was to investigate the differential effects of a 6-week treatment with either atorvastatin 20 mg/d alone (n = 19) or micronized fenofibrate 200 mg/d alone (n = 19) on inflammation, cell adhesion, and oxidation markers in type 2 diabetes mellitus subjects with marked hypertriglyceridemia. In addition to the expected changes in lipid levels, atorvastatin decreased plasma levels of C-reactive protein (-26.9%, P = .004), soluble intercellular adhesion molecule 1 (-5.4%, P = .03), soluble vascular cell adhesion molecule 1 (-4.4%, P = .008), sE-selectin (-5.7%, P = .02), matrix metalloproteinase 9 (-39.6%, P = .04), secretory phospholipase A(2) (sPLA(2)) (-14.8%, P = .04), and oxidized low-density lipoprotein (-38.4%, P < .0001). On the other hand, fenofibrate had no significant effect on C-reactive protein levels and was associated with reduced plasma levels of sE-selectin only (-6.0%, P = .04) and increased plasma levels of sPLA(2) (+22.5%, P = .004). These results suggest that atorvastatin was potent to reduce inflammation, oxidation, and monocyte adhesion in type 2 diabetes mellitus subjects with marked hypertriglyceridemia, whereas fenofibrate decreased sE-selectin levels only and was associated with an elevation of sPLA(2) levels.
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PMID:Differential effect of atorvastatin and fenofibrate on plasma oxidized low-density lipoprotein, inflammation markers, and cell adhesion molecules in patients with type 2 diabetes mellitus. 1824 11

Early identification of acute coronary syndrome (ACS) is important to guide therapy at a time when it is most likely to be of value. In addition, predicting future risk helps identify those most likely to benefit from ongoing therapy. Cardiac troponin T (cTnT) is useful for both purposes although cannot reliably rule out ACS until 12 hours after pain onset and does not fully define future risk. In this review article we summarize our previously published research, which assessed the value of myocyte injury, vascular inflammation, hemostatic, and neurohormonal markers in the early diagnosis of ACS and risk stratification of patients with ACS. In addition to cTnT, we measured heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, high-sensitivity C-reactive protein, myeloperoxidase, matrix metalloproteinase 9, pregnancy-associated plasma protein-A, D-dimer, soluble CD40 ligand, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Of the 664 patients enrolled, 415 met inclusion criteria for the early diagnosis of acute myocardial infarction (MI) analysis; 555 were included in the risk stratification analysis and were followed for 1 year from admission. In patients presenting <4 hours from pain onset, initial H-FABP had higher sensitivity for acute MI than cTnT (73% vs. 55%; P=0.043) but was of no benefit beyond 4 hours when compared to cTnT. On multivariate analysis, H-FABP, NT-proBNP, and peak cTnT were independent predictors of 1-year death/MI. Our research demonstrated that, in patients presenting within 4 hours from pain onset, H-FABP may improve detection of ACS. Measuring H-FABP and proBNP may help improve long-term risk stratification.
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PMID:Investigation of a multimarker approach to the initial assessment of patients with acute chest pain. 1947 67

Few studies have assessed the incremental usefulness of multimarkers as predictors of cardiovascular events in patients with mild to moderate coronary artery lesions.We examined 9 plasma inflammatory cytokines (cathepsin S, CXCL16, sopluble CD40 ligand, interleukin-10, placental growth factor, GDF15, matrix metalloproteinase 9, monocyte chemoattractant protein-1, and high-sensitivity C-reactive protein) in 964 patients showing mild to moderate lesions and assessed their association with risk of cardiovascular events during 3 years of follow-up (median 17 months).In a backward Cox regression procedure, Cystatin S (hazard ratio [HR]: 1.788, 95% CI: 1.233 to 2.593, P = 0.02), soluble CD40 ligand (HR: 1.255, 95% CI: 1.054 to 1.494, P = 0.011), placental growth factor (HR: 1.194, 95% CI: 0.976 to 1.461, P = 0.035), and GDF15 (HR: 0.725, 95% CI: 0.550 to 0.956, P = 0.023) were significantly related to cardiovascular events. Compared with multimarker score (according to regression coefficients of significant biomarkers) in the lowest two quintiles, patients in the highest quintile had a higher risk of cardiovascular events after adjustment for traditional risk factors (HR: 2.77, 95% CI: 1.30 to 5.87, P = 0.008). Adding the multimarker score to traditional risk factors contributed significantly to the prediction of cardiovascular events (AUC increased from 0.67 to 0.72).A multimarker approach added to the predictive information obtained from traditional risk factors in patients with mild to moderate coronary artery lesions.
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PMID:Multimarker approach for the prediction of cardiovascular events in patients with mild to moderate coronary artery lesions. A 3-year follow-up study. 2268 11

Despite a recent health claim by the European Agency on Food Safety, the effect of high doses of dietary monacolin supplements from red yeast rice on cholesterolemia has not been tested in Italian subjects. Our aim via a crossover, double-blind, placebo-controlled randomized clinical trial was to test if a short-term treatment with 10 mg monacolins could improve lipid pattern, high-sensitivity C-reactive protein (hs-CRP), and vascular remodeling biomarkers in a small cohort of Mediterranean subjects. Thus, 25 healthy, mildly hypercholesterolemic subjects were enrolled, and after 4 weeks of a stabilization diet, subjects were randomized to the sequence placebo-washout-monacolins or monacolins-washout-placebo, with each period being 4 weeks long. At each study step, a complete lipid pattern, safety parameters, hs-CRP, and matrix metalloproteinases 2 and 9 levels were measured. When compared to the placebo group, monacolins-treated patients experienced a more favorable percent change in total cholesterol (-12.45%, 95% CI -16.19 to -8.71), low-density lipoprotein cholesterol (-21.99%, 95% CI -26.63 to -17.36), non-high-density lipoprotein cholesterol (-14.67%, 95% CI -19.22 to -10.11), matrix metalloproteinase 2 (-28.05%, 95% CI -35.18 to -20.93), matrix metalloproteinase 9 (-27.19%, 95% CI -36.21 to -18.15), and hs-CRP (-23.77%, 95% CI -30.54 to -17.01). No significant differences were observed in regards to triglycerides, high-density lipoprotein cholesterol, and safety parameters. On the basis of our data, we demonstrate that a 10-mg monacolin nutraceutical appears to safely reduce cholesterolemia, hs-CRP, and markers of vascular remodeling in Italian subjects. These results have to be confirmed in larger patient samples and longer studies.
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PMID:Red yeast rice improves lipid pattern, high-sensitivity C-reactive protein, and vascular remodeling parameters in moderately hypercholesterolemic Italian subjects. 2389 Mar 51

There is still no "gold standard" for the diagnosis and prognosis of post-operative periprosthetic joint infection (PJI). Among serum biomarkers, an emerging molecule is presepsin, the soluble fraction of CD14, recently described in other settings as a powerful diagnostic tool to detect sepsis at different degrees of severity. The aim of this study was to investigate the diagnostic and prognostic value of presepsin in PJI. A total of 30 patients with PJI and 30 patients without PJI were enrolled. Presepsin, C-reactive protein (CRP), serum interleukin (IL)-6, triggering receptor expressed on myeloid cells 1 (TREM-1), CCL2, matrix metalloproteinase 9 (MMP-9), CD163, osteopontin (OPN), and toll-like receptor 2 (TLR2) were measured at different times after surgery. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker. Presepsin showed greater diagnostic value than CRP and IL-6; CD163, TREM-1, and MMP-9 had very low diagnostic potential. Presepsin, OPN, CCL2, suPAR, and TLR2 all decreased significantly with increasing time of recovery after surgery in PJI patients. Presepsin can be considered a useful tool for the diagnosis and clinical monitoring of PJI and can be backed by a panel of new inflammatory markers involved in monocyte-/macrophage-mediated inflammatory responses, such as OPN, CCL2, TLR2, and suPAR.
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PMID:Presepsin: A potential biomarker of PJI? A comparative analysis with known and new infection biomarkers. 2925 Oct

Classical risk factors for endothelial dysfunction (ED), such as age, gender, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, and smoking history are utilised for the Framingham score and Systemic Coronary Risk Estimation (SCORE) for evaluation of the 10-year cardiovascular risk in routine practice. Nonetheless, pro-inflammatory mediators are deeply involved in the initiation and the progression of ED and coronary artery disease (CAD), and act additionally or independently of metabolic factors before clinical manifestations of the disease appear. C-reactive protein, a marker of intimal thickening of the myeloid-related protein 8/14 heterodimer, monocyte chemotactic protein 1, interleukin-15, the cytotoxic mediator, granulysin, and the matrix metalloproteinase 9 could be valuable, single, fast, and non-invasive laboratory tools for ED deterioration degree assessment. We propose to investigate the impact of pro-inflammatory biomarkers on ED, measured by previously established clinical methods in patients with yet undiagnosed CAD and at medium risk for an acute coronary event. It could be useful to measure and correlate the concentration of particular inflammatory markers in peripheral blood samples and the results of the Framingham and SCORE charts, multi-slice computed tomography coronary angiography, echocardiography, brachial artery flow-mediated dilatation, carotid-femoral pulse wave velocity, ankle-brachial index, carotid wall thickening, myocardial perfusion scintigraphy, and particularly, cardiac magnetic resonance imaging. The goal would be that the degree of correlation between particular inflammatory markers and the results of some methods for the assessment of ED or cardiac ischaemic imaging could be emphasised and pro-inflammatory markers positioned in the pathogenetic algorithm of CAD.
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PMID:Correlation between immunological-inflammatory markers and endothelial disfunction in the early stage of coronary heart disease. 2968 2

Recombinant tissue plasminogen activator (rt-PA) can be utilized to treat ischemic stroke with safety and effectiveness but limited by a narrow therapeutic window. In the present clinical trial among patients with stroke, we sought to evaluate the potential of fisetin to extend the therapeutic window of rt-PA treatment. Patients with stroke were divided based on their onset-to-treatment time (OTT) and then randomly assigned to receive the rt-PA treatment combined with fisetin or placebo. Primary outcome was evaluated using the National Institutes of Health Stroke scale (NIHSS), and secondary outcome was assessed by serum levels of matrix metalloproteinase (MMP) 2, MMP 9, and C-reactive protein (CRP). Fisetin dramatically improved the treatment outcomes of the patients with stroke in the delayed OTT strata, as revealed by lower NIHSS scores. The beneficial effect of fisetin was likely attributable to reduced levels of MMP-2, MMP-9, and CRP in the serum, as evidenced by strong linear correlations between serum levels of such markers with the NIHSS scores in all enrolled patients. Fisetin may possess the potential to supplement traditional rt-PA treatments among patients with stroke, particularly for those with delayed OTT, and thereby extend the otherwise narrow therapeutic window and improve the treatment outcomes.
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PMID:Fisetin Prolongs Therapy Window of Brain Ischemic Stroke Using Tissue Plasminogen Activator: A Double-Blind Randomized Placebo-Controlled Clinical Trial. 3143 98


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