Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma fibrinolytic/proteolytic balance was assessed in 60 stable angina patients who underwent control coronary catheterization and the results were correlated with angiographic findings and control samples (n = 20). The concentrations of t-PA, PAI-1, collagenase (MMP-1), tissue inhibitor of MMP (TIMP-1), plasmin-antiplasmin (PAP) complexes and alpha2-macroglobulin (alpha2-M) were measured in plasma samples. The results showed a significant increase of PAP (p <0.001) and a reduction of alpha2-M (p <0.001) in the group of patients when compared to controls, indicating a degree of fibrinolysis/proteolysis activation. There was no correlation between the different parameters analyzed and the extent of angiographically proven atherosclerosis (one or more stenotic vessels), while the t-PA levels were significantly elevated (p <0.03) in patients with coronary stenosis > or =75% or occlusion. We conclude that there is a disturbance of the plasma fibrinolysis/proteolysis in patients with stable angina not related to the extent of atherosclerosis. The t-PA levels may be a good marker for coronary occlusion in these patients.
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PMID:Fibrinolysis/proteolysis balance in stable angina pectoris in relation to angiographic findings. 1152 15

Previous experimental studies have demonstrated that MMPs (matrix metalloproteinases) contribute to LV (left ventricular) remodelling. We hypothesized that cardiac MMPs are activated in patients with AMI (acute myocardial infarction) and, if so, MMP production may be attenuated by statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) through their cardiovascular protective actions. We studied 30 patients, ten control patients with stable angina pectoris and 20 patients with AMI, in whom LV catheterization at the chronic stage was performed 22+/-12 days (value is mean+/-S.D.) after the onset of AMI. Blood samples were collected from the CS (coronary sinus) and a peripheral artery. In patients with AMI, the levels of MMP-2 and MMP-9 were significantly (P<0.05) higher in the CS than the peripheral artery (MMP-2, 853+/-199 compared with 716+/-127 ng/ml; MMP-9, 165+/-129 compared with 98+/-82 ng/ml), whereas no significant differences were observed in the patients with angina pectoris. The CS-arterial concentration gradients of MMP-2 and MMP-9 correlated positively with BNP (brain natriuretic peptide) levels (MMP-2, R=0.68, P<0.01; MMP-9, R=0.59, P<0.05) and LV end-diastolic volume index (MMP-2, R=0.70, P<0.01; MMP-9, R=0.70, P<0.01). When patients with AMI treated with 10 mg of pravastatin or without (n=10 in each group) were compared, this statin therapy significantly (P<0.05) decreased the CS-arterial concentration gradients of MMP-2 (69+/-43 compared with 213+/-185 ng/ml) and MMP-9 (14+/-27 compared with 119+/-84 ng/ml). In conclusion, the enhanced production of cardiac MMP-2 and MMP-9 is associated with LV enlargement and elevated BNP levels in patients with AMI. A pleiotropic effect of statins appears to be associated with the modulation of cardiac MMP activation, which may be potentially beneficial in the attenuation of post-infarction LV remodelling.
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PMID:Enhanced cardiac production of matrix metalloproteinase-2 and -9 and its attenuation associated with pravastatin treatment in patients with acute myocardial infarction. 1693 10

Inflammation and ECM (extracellular matrix) remodelling play important roles in LV (left ventricular) remodelling following acute MI (myocardial infarction). Previous studies show elevated plasma MMP (matrix metalloproteinase) levels in patients with acute MI, but their sources are not clear. The recruitment of mononuclear cells into the infarcted myocardium is critical for inflammatory responses, but their exact roles in LV remodelling have not been fully investigated, as it is difficult to isolate and study the function of regional inflammatory cells. To address these questions, we isolated PBMCs (peripheral blood mononuclear cells) from blood samples of patients with acute MI or stable angina, or healthy controls (n=14, 8 and 12 respectively). PBMCs were cultured for 24 h and the MMP9 level in the culture medium was measured by gelatin zymography, and MMP9 gene expression was measured by real-time PCR. Two superarrays (ECM and adhesion molecules, and common cytokines; 84 genes included in each array) were employed to screen gene expression profiles by PBMCs in five patients with acute MI and five controls. We found that MMP9 expression by PBMCs at both the mRNA and protein levels was increased 2-fold (both P<0.05) in patients with acute MI compared with the two control groups. Notably, MMP2 was not expressed by PBMCs. Superarray screening revealed that PBMCs not only expressed MMPs, TIMPs (tissue inhibitors of metalloproteinases) and matrix proteins, but also served as an important source of cell adhesion molecules, inflammatory cytokines and growth factors. A total of 42 genes were differentially expressed in patients with acute MI compared with controls. Expression of selected genes was confirmed by real-time PCR. In conclusion, PBMCs constitute a key cellular source for elevated plasma MMP9, but not for MMP2. PBMCs also contribute to systemic and regional inflammation and matrix remodelling in acute MI.
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PMID:Activation of peripheral blood mononuclear cells and extracellular matrix and inflammatory gene profile in acute myocardial infarction. 2038 21

Circulating interleukin-18 (IL-18) is thought to promote atherosclerosis and cardiovascular complications such as plaque rupture. Atherosclerosis is also characterized by smooth muscle cell migration, a consequence of extracellular matrix (ECM) degradation regulated by metalloproteinases (MMPs). Because extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote plaque instability by inducing ECM degradation and MMP synthesis, we investigated whether a cross-regulatory interaction exists between IL-18 and EMMPRIN in human monocytes. EMMPRIN levels in monocytes were markedly greater in 20 patients with acute myocardial infarction (AMI) compared with 20 patients with stable angina pectoris or 20 healthy volunteers (control group). The levels of IL-18 and MMP-9 in serum were also significantly greater in the AMI group in comparison with the other 2 groups. IL-18 levels positively correlated with increased levels of EMMPRIN in monocytes. In vitro, the expression of EMMPRIN was increased in monocytes cultured with IL-18, and IL-18 secretion was augmented in monocytes cultured with EMMPRIN. Gene silencing of EMMPRIN by small interfering RNA reduced monocyte secretion of both IL-18 and MMP-9. In the present study, cross-regulation between IL-18 and EMMPRIN in monocytes was demonstrated. This interaction may amplify the inflammatory cascade and be responsible for increased monocytic MMP-9 serum levels in atherosclerosis, contributing to atherosclerotic plaque destabilization and subsequent AMI.
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PMID:Interleukin 18 and extracellular matrix metalloproteinase inducer cross-regulation: implications in acute myocardial infarction. 2526 95