Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed an observational study on 137 patients undergoing carotid endarterectomy (CEA). Patients on statins were less likely to have had symptoms in the 4 weeks before CEA (p = 0.0049) and were less likely to have spontaneous cerebral embolization detected by transcranial Doppler (p = 0.0459). Carotid plaques retrieved at CEA from patients taking statins revealed significantly lower concentrations of matrix metalloproteinase-1 (p = 0.0176), matrix metalloproteinase-9 (p = 0.0018), and interleukin-6 (p = 0.0005).
Am J Cardiol 2004 Jul 01
PMID:Comparison of levels of matrix metalloproteinases, tissue inhibitor of metalloproteinases, interleukins, and tissue necrosis factor in carotid endarterectomy specimens from patients on versus not on statins preoperatively. 1521 30

The relation between matrix metalloproteinase-1 promoter genotype and remodeling was studied in 42 patients after their first acute myocardial infarctions. Patients possessing 2 GG alleles were at increased risk for remodeling compared with homozygotes for the G allele and heterozygotes possessing 1 G and 1 GG allele.
Am J Cardiol 2004 Oct 15
PMID:Matrix metalloproteinase-1 promoter polymorphisms and changes in left ventricular volume following acute myocardial infarction. 1547 22

Despite major advancements in the technology used for the percutaneous treatment of coronary artery disease, chronic total occlusions (CTOs) persist as a major challenge to the interventional cardiologist with relatively low success rates. CTOs are evident in 20% of patients undergoing cardiac catheterization and are responsible for the majority of cases that are referred to bypass surgery. There is growing evidence that patients may benefit from recanalization of a CTO by alleviation of angina, improving left ventricular function, and potentially long-term survival. The major obstacle to percutaneous recanalization of CTOs is the inability to cross the occlusion with coronary guidewires. Even when crossed, the operator has to deal with the exact location of the distal wire (e.g., dissection or true lumen) and the existence of relatively long lesion requiring multiple stents with high restenosis rates. New technologies for CTO revascularization have been focused mainly on a mechanical approach including specialized guidewires and more recently, specific devices using highly sophisticated technology such as laser guidewire, optical coherence reflectometry, and a blunt microdissection catheter. An alternate biological approach involves the local administration of enzymes such as plasminogen activators (urokinase) or collagenase, which can act locally to specifically degrade the collagen content of the CTO, thereby "softening" the occlusion and allowing easier guidewire crossing. In conclusion, CTOs emerge as a great technical challenge and are the focus of novel series of mechanical and biological approaches.
J Interv Cardiol 2004 Dec
PMID:Novel approaches for the treatment of chronic total coronary occlusions. 1554 94

We investigated the association between serum levels of matrix metalloproteinase-1 (MMP-1) and coronary artery disease (CAD) in 185 patients who underwent elective coronary angiography. MMP-1 levels did not differ between patients who had CAD and those who did not and did not correlate with the number of >50% stenotic vessels or segments, but MMP-1 levels were significantly higher in patients who had CAD and complex coronary lesions than in those who did not have such lesions and those who did not have CAD. High serum levels of MMP-1 were associated with the presence of complex lesions in patients who had CAD.
Am J Cardiol 2005 Jan 01
PMID:Levels of matrix metalloproteinase-1 in patients with and without coronary artery disease and relation to complex and noncomplex coronary plaques. 1561 98

Left ventricular (LV) remodeling following myocardial infarction (MI) is a complex process involving extracellular matrix degradation and fibrosis. While early remodeling is beneficial, chronic remodeling leads to decompensated heart failure (HF). We assessed the hypothesis that activation of the plasminogen-MMP system is involved in the remodeling of the infarct scar and compared it to the remaining viable myocardium. MI was induced by coronary artery ligature in 42 male Wistar rats. Three months following surgery, animals were divided into compensated (n=26) or decompensated (n=16) groups and compared to sham-operated rats (n=17). Scar and remaining viable LV myocardium (LVM) were separately analyzed for MMP-2, -7, -9, urokinase type and tissue type plasminogen activator (uPA and tPA) mRNA levels by RT-PCR. Their protein or activity levels, plus those of plasminogen/plasmin, tissue inhibitor of metalloproteinase-1, -2, -4 (TIMP-1, -2, -4) and plasminogen activator inhibitor-1 (PAI-1) were analyzed in tissue conditioned media by Western blot, ELISA and/or zymography. MMP and plasmin proteolytic activities were increased in the scar as compared to paired LVM thus indicating that activation of plasminogen and pro-MMPs is a key event in scar tissue remodeling. MMP and plasminogen activators (uPA, tPA) mRNAs were increased accordingly. Furthermore, inhibitors of the proteolytic enzymes, TIMP-1 and PAI-1 were increased in the scars from failing hearts and LVM thus suggesting a dynamic interplay between proteolysis and its inhibitors. This study shows a high degree of activation of the MMP-plasminogen system and the balance with their inhibitors in the infarcted myocardium, and suggests that this activation participates more to the remodeling of the scar tissue than to the remaining myocardium.
J Mol Cell Cardiol 2005 Jan
PMID:The plasminogen-MMP system is more activated in the scar than in viable myocardium 3 months post-MI in the rat. 1562 36

There is ample evidence supporting the view that alterations in the balance between matrix deposition and matrix degradation brought about by changes in the respective activities of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) contribute significantly to cardiac dysfunction and disease. Here we show that TIMP-1 was upregulated up to threefold after treatment with the inflammatory mediator and gp130 ligand oncostatin M (OSM) in human adult cardiac myocytes and fibroblasts. The Erk1/2 inhibitor PD98059 and the p38 inhibitor SD202190 abolished the effect of OSM on TIMP-1 production in both cell types. Human cardiac myocytes and human cardiac fibroblasts also express MMP-1, 2, 3 and 9, and TIMP-2 constitutively. OSM, however, did not affect the expression of these proteins. In addition also the other gp130 ligands tested, cardiotrophin-1 (CT-1), interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) had no effect on the expression of TIMPs and MMPs studied. We speculate that OSM by inducing TIMP-1 expression counteracts excessive proteolysis and unrestricted matrix degradation during inflammatory processes in the heart. The notion that OSM favors matrix stabilization in the human heart is further supported by our earlier observation that OSM also upregulates PAI-1, the physiological inhibitor of the protease urokinase-type PA (u-PA), which in turn is essential for extracellular proteolysis. Therefore we propose a role for the gp130 ligand OSM in the modulation of cardiac remodeling and repair processes.
J Mol Cell Cardiol 2005 Sep
PMID:The gp130 ligand oncostatin M regulates tissue inhibitor of metalloproteinases-1 through ERK1/2 and p38 in human adult cardiac myocytes and in human adult cardiac fibroblasts: a possible role for the gp130/gp130 ligand system in the modulation of extracellular matrix degradation in the human heart. 1589 Mar 57

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a predictor of left ventricular remodeling. Matrix metalloproteinases (MMPs) contribute to collagen breakdown that is associated with ventricular remodeling after acute myocardial infarction (AMI). We assessed the association between circulating levels of NT-pro-BNP, MMP-2, and MMP-9 and their inhibitor (tissue inhibitor of metalloproteinase-1) early (24 and 72 hours) and late (7 and 30 days) after AMI in 108 patients who had ST-elevation AMI (90 men; mean age 60 years). Serum MMP-2 levels measured 24 and 72 hours after AMI were inversely associated with NT-pro-BNP levels, whereas MMP-9 serum levels were positively related. During late-stage remodeling after AMI, circulating concentrations of tissue inhibitor of metalloproteinase-1 were independently associated with NT-pro-BNP levels 7 and 30 days after AMI. This study shows that, in patients who have ST-elevation AMI, circulating levels of NT-pro-BNP are associated with MMPs in a species-specific and time-dependent manner.
Am J Cardiol 2005 Jul 01
PMID:N-terminal pro-B-type natriuretic peptide and matrix metalloproteinases in early and late left ventricular remodeling after acute myocardial infarction. 1597 28

Hepatocyte growth factor (HGF) is a potent regeneration factor for endothelial and epithelial cells, and has also been shown to modulate extracellular matrix synthesis and matrix metalloproteinase activity in renal epithelial cells and tumor cells. Controversial results have been published concerning the possible role of HGF in the pathogenesis of coronary atherosclerosis. In this study, we have investigated the effect of oxidized low density lipoproteins (LDL) and elevated glucose concentrations on HGF synthesis in cultured human coronary artery smooth muscle cells. In addition, we have studied whether HGF modulates the release of extracellular matrix, extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinases (MMP) by coronary artery smooth muscle cells. Oxidized LDL (1-10 microg/ml) induced a significant dose-dependent decrease of HGF release and a concomitant decrease of HGF mRNA expression, whereas native LDL and elevated glucose concentrations induced no significant changes of HGF synthesis. Incubation of cultured human coronary smooth muscle cells with human HGF (1-100 ng/ml) did not significantly alter cell migration and collagen I, fibronectin, EMMPRIN, MMP-1, MMP-2 and MMP-9 release. In summary, our results provide evidence that HGF does not promote coronary plaque growth or plaque destabilization. Regarding the fact that HGF is a potent endothelial cell regeneration factor, the observed downregulation of HGF synthesis by oxidized LDL supports the concept that HGF might be a protective factor in coronary atherosclerosis and that a decrease rather than an increase of HGF synthesis might promote coronary atherosclerosis.
Int J Cardiol 2005 Sep 01
PMID:Oxidized LDL inhibit hepatocyte growth factor synthesis in coronary smooth muscle cells. 1609 93

Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting. Atrial remodeling has been observed in AF and has been associated with the development of this arrhythmia. Because 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) have been demonstrated to modify remodeling, we hypothesized a protective role of statins against postoperative AF. We also hypothesized that extracellular matrix turnover and brain natriuretic peptide (BNP) might be related to such atrial remodeling. We studied 234 consecutive patients who underwent coronary artery bypass grafting (173 men; 65 +/- 9 years of age) in whom the occurrence of postoperative AF was monitored. In a subgroup of 66 patients, we measured plasma levels of matrix metalloproteinase-1 (MMP-1), its inhibitor, tissue inhibitor matrix metalloproteinase-1 (TIMP-1; as indexes of extracellular matrix remodeling), and N-terminus pro-BNP (related to left ventricular function) at baseline and at 24 hours after surgery. Of 234 patients, 66 (28.2%) developed postoperative AF. In multivariate analysis, previous AF was related to an increase in the development of AF (odds ratio 11.92, 95% confidence interval 2.37 to 59.98, p = 0.026), whereas statin use was related to a decrease in arrhythmia (odds ratio 0.52, 95% confidence interval 0.28 to 0.96, p = 0.038). A higher TIMP-1/MMP-1 ratio at 24 hours after surgery was present in those who did not develop postoperative AF (p = 0.043). Statin use was associated with increased TIMP-1 levels and TIMP-1/MMP-1 ratio (p = 0.027 and 0.036, respectively). No significant relations to N-terminus pro-BNP were seen. In conclusion, previous AF and nonuse of statins are significantly associated with AF after coronary artery bypass grafting. Statin use may be protective against AF after coronary artery bypass grafting, possibly due to alterations in the extracellular matrix and remodeling after coronary artery bypass grafting.
Am J Cardiol 2006 Jan 01
PMID:Statins and postoperative risk of atrial fibrillation following coronary artery bypass grafting. 1667 8

Mutations in the gene for fibrillin-1 cause Marfan syndrome (MFS), a common hereditary disorder of connective tissue. Recent findings suggest that proteolysis, increased matrix metalloproteinase activity, and fragmentation of fibrillin-rich microfibrils in tissues of persons with MFS contribute to the complex pathogenesis of this disorder. In this study we show that a fibrillin-1 fragment containing a EGFEPG sequence that conforms to a putative GxxPG elastin-binding protein (EBP) consensus sequence upregulates the expression and production of matrix metalloproteinase (MMP)-1 by up to ninefold in a cell culture system. A mutation of the GxxPG consensus sequence site abrogated the effects. This is the first demonstration of such an effect for ligands other than elastin fragments. Molecular dynamics analysis of oligopeptides with the wildtype and mutant sequence support our biochemical results by predicting significant alterations of structural characteristics such as the potential for forming a type VIII beta-turn that are thought to be important for binding to the EBP. These results suggest that fibrillin-1 fragments may regulate MMP-1 expression, and that the dysregulation of MMPs related to fragmentation of fibrillin might contribute to the development of MFS. Our Gene Ontology (GO) analysis of the human proteome shows that proteins with multiple GxxPG motifs are highly enriched for GO terms related to the extracellular matrix. Matrix proteins with multiple GxxPG sites include fibrillin-1, -2, and -3, elastin, fibronectin, laminin, and several tenascins and collagens. Some of these proteins have been associated with disorders involving alterations in MMP regulation, and the results of the present study suggest a potential mechanism for these observations.
J Mol Cell Cardiol 2006 Feb
PMID:A fibrillin-1-fragment containing the elastin-binding-protein GxxPG consensus sequence upregulates matrix metalloproteinase-1: biochemical and computational analysis. 1644 22


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