Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Healing of myocardial infarction is associated with hypertrophy of a region surrounding the scar. In order to characterize the pattern of regional hypertrophy after healing of small myocardial infarctions, we used a Coulter Channelyzer to measure directly regional cell volume and light microscopy to measure cell length of isolated myocytes. Acute left ventricular myocardial infarctions were surgically created in adult cat hearts. After healing for 10.4 +/- 5.0 months, cells were dissociated by collagenase perfusion. Myocardial cells were isolated from three regions of the infarcted ventricle and the same three anatomical regions of unoperated control hearts: (1) remote from the infarct, (2) non-scarred tissues adjacent to the infarct, and (3) from the infarct. The volume of cells from control hearts was correlated significantly with individual body weight resulting in large inter-animal variations, but small intra-animal variations. Inter-animal comparisons were made by normalizing adjacent and infarct regions to percent change from its remote region. Myocyte volumes from hearts with healed infarcts were increased by 31% in the infarct region and by 20% in the adjacent region, relative to the corresponding regions from control hearts (P less than 0.05). Cell lengths were not different from control in any region. Calculated cross-sectional areas followed the same pattern as was observed for cell volumes. We conclude that there is a region of hypertrophy surrounding a small, transmural healed myocardial infarction that is characterized by increased myocyte cross sectional area with no change in cell length. This pattern is typical of the concentric hypertrophy observed with pressure overload rather than eccentric hypertrophy observed with volume overload.
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PMID:Regional increase in isolated myocyte volume in chronic myocardial infarction in cats. 183 2

Myocardial extracellular matrix is organized into a complex arrangement of intercellular and pericellular fibres and fibrils that serves as a supporting framework for contracting cells. Recent evidence suggests that changes in ventricular shape and function occurring after ischaemic injury may be related to alterations of this matrix. In this report we describe the rapid and extensive loss of collagen in myocardial infarction produced by ligating the left anterior descending coronary artery of the rat for 1-3 h. The total collagen content in the myocardial infarct zones after 1, 2 and 3 h of ligation was 75 +/- 8%, 65 +/- 7% and 50 +/- 10% respectively (mean +/- S.D.) of that of either the non-infarcted tissue controls or of the same regions in sex- and age-matched normal left ventricles. A marked decrease also occurred in the residual collagens which were not extractable with 6 M-guanidine hydrochloride, suggesting that rapid degradation of insoluble collagen fibres may also occur. The decreased collagen content in the 3 h myocardial infarct coincided with the appearance of several enzyme activities. Collagenase, other neutral proteinase and presumed lysosomal serine proteinase activities were increased by 3, 3 and 2 times the control values respectively. These results suggest that the increased activities of collagenase and other neutral proteinases may be responsible for the rapid degradation of extracellular matrix collagen in myocardial infarct.
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PMID:Collagen degradation in ischaemic rat hearts. 215 82

A total of 46 patients, aged 39-71 years (mean 57.7), were studied. Forty-eight percent of the patients were hyperlipidemic and 63% had earlier suffered a myocardial infarction. Biopsies from aorta were obtained during coronary bypass surgery. Apo B was extracted from the intima by incubation of the tissue in buffer, followed by collagenase digestion. Intimal apo B was quantified in an immunoradiometric assay. There were significant correlations between total or collagenase-extractable apo B and serum cholesterol (rs = 0.39, P less than 0.01), serum triglycerides (rs = 0.33, P less than 0.05), LDL cholesterol (rs = 0.33, P less than 0.05) and serum apo B (rs = 0.37, P less than 0.05). The correlations were strongest for the collagenase-extractable apo B, while no correlations were observed for the buffer-extractable intimal apo B. No significant correlations were found between intimal apo B and serum HDL, apo A-I, smoking habits, history of hypertension or sustained myocardial infarction. Follow-up data were available for 42 of the patients, with a mean follow-up period of 35.1 months. The patients were classified according to symptoms of angina pectoris at the time of follow-up. There were significantly lower levels of serum apo A-I in the patients with poorer clinical prognosis. In a linear multiple stepwise regression analysis, apo A-I and serum LDL were significantly and independently related to clinical prognosis (R2 = 0.31).
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PMID:Apolipoprotein B in human aortic biopsies in relation to serum lipids and lipoproteins. 278 44

Activity of collagen peptidase was measured in patients with myocardial infarction. Determinations were carried out 1, 3, 6, 9, 14 and 21 days after admission to the hospital. A decrease of activity was observed between the 6th-21st day of the disease. A low correlation with serum aminotransferases was found. It is concluded that estimation of serum collagen peptidase does not reflect accumulation of collagen in the healing heart muscle.
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PMID:Collagen peptidase in serum of patients with myocardial infarction. 329 85

Collagen which is present in the myocardium in relatively small amounts is the most abundant structural protein of the connective tissue network. Its structural organization consists of a complex weave of collagen fibers that surrounds and interconnects myocytes, groups of myocytes, muscle fibers and muscle bundles. The conformation of interstitial fibrillar collagen makes it highly resistant to degradation by all proteinases other than specific collagenases. In hearts with myocardial damage secondary to myocardial infarction, chronic ischemia, inflammation, or cardiomyopathy, a complex sequence of compensatory events occur that eventually result in an adverse left ventricular remodeling. This continual state of remodeling is characterized by persistent collagenase activity, fibrillar collagen degradation, and progressive myocyte loss. The net effect is a shift in the balance between collagen synthesis and degradation which leads to an inadequate fibrillar collagen matrix, progressive ventricular dilatation and sphericalization with wall thinning and eventual congestive heart failure.
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PMID:Ventricular remodeling in heart failure: the role of myocardial collagen. 854 Apr 1

Cardiac fibroblasts appear to be important in producing and maintaining the extracellular matrix (ECM) of the heart. The abnormal proliferation of cardiac fibroblasts and deposition of the ECM protein, collagen, associated with hypertension and myocardial infarction, may adversely affect the performance of the heart. Several groups of factors affect collagen gene expression and/or growth of cardiac fibroblasts. Angiotensin II, aldosterone and endothelins play a central role in the remodeling of the ECM in hypertension, and decrease collagenase activity and/or increase collagen synthesis in cultured cells. Regulatory peptides that are generally elevated at sites of injury, such as TGF-beta 1 and PDGF, increase collagen synthesis and/or stimulate mitogenesis. Mechanical stretch enhances collagen expression and cell proliferation, responses which could in part be due to integrin activation. Cytokines may stimulate or inhibit cell growth, the latter through prostaglandin formation. Angiotensin II is a principal determinant in vivo of cardiac fibroplasia and synthesis of the ECM proteins, collagen and fibronectin. Cardiac fibroblasts possess G-protein-coupled AT1 receptors for angiotensin II that couple to activation of multiple signalling pathways, including: phospholipase C-beta, with the subsequent release of Ca2+ from intracellular stores and activation of protein kinase C, mitogen-activated protein kinases, tyrosine kinases, phospholipase D, phosphatidic acid formation, and the STAT family of transcription factors. Cardiac fibroblasts respond to angiotensin II with hyperplastic/hypertrophic growth, and increased expression of collagen, fibronectin, and integrins. The mechanisms by which the AT1 receptor activates multiple signalling pathways are not known, although the receptor might interact at some level with both integrins and cytokine receptors. Different signalling pathways of the AT1 receptor may subserve different cellular responses, such as mitogenesis, ECM synthesis, or an inflammatory/stress response. Crosstalk among the signalling pathways of the AT1 receptor, and those of G-protein, cytokine, and growth-factor receptors, may determine the ultimate response of the cell.
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PMID:Molecular signalling mechanisms controlling growth and function of cardiac fibroblasts. 857 2

The characteristics of a subset of atherosclerotic plaques that is responsible for myocardial infarction (infarctogenic plaques) are increasingly well defined. They include moderate size, a thin fibrous cap, and a large lipid pool. Fissuring of the cap leads to thrombotic occlusion and often to an acute coronary event. Physical stresses on, and proteolytic weakening of, the cap--both related to effects of hyperlipidemia on the plaque--increase the risk of fissuring. Treatment of hyperlipidemia leads to regression of experimental atherosclerosis, promotes regression and reduces progression of human coronary artery disease. The arterial changes in humans are predictive of reduced incidence of coronary events. This sequence of events may reflect gradual depletion of plaque lipids, and also a more rapid depletion of chronic inflammatory cells in the plaque cap that are the source of collagenase and other proteases. The primary objective of lipid-lowering therapy appears to be the induction of these changes in infarctogenic plaques, and vigorous treatment should be targeted on patients likely to harbor such plaques.
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PMID:Coronary heart disease prevention and the infarctogenic plaque. 868 41

In the normal myocardium matrix metalloproteinases (MMP) are present in the latent form. To examine whether MMP are activated following infarction or idiopathic dilated cardiomyopathy (DCM), we extracted and measured MMP activity in tissue derived from 7 explanted, failing human hearts due to either previous myocardial infarction (MI) or DCM. MMP activity in infarcted left ventricle (LV), noninfarcted LV and right ventricle (RV) from MI patients, as well as tissue from either ventricle of DCM patients, were compared to the activity of donor heart tissue. SDS-PAGE and dye-binding assays were used to determine total protein concentration, while collagenase activity was measured by SDS-PAGE type substrate gels embedded with type I gelatin (zymography). Accuracy of the zymographic technique was shown for tissue samples as small as 0.05 mg and was comparable to results obtained by a spectrophotometric method. After normalization for total protein concentration, we found 3 +/- 1% collagenase activity in normal atrial tissue which could be activated to 80-90% by trypsin or plasmin, indicating that collagenase is normally inactive or in a latent form in human heart. In endo- and epimyocardium of infarcted LV, on the other hand, collagenase activity was 85-95% and 10-20%, respectively, while 5-10% and 3-5%, respectively, in noninfarcted LV. In DCM, collagenolytic activity in the endo and epimyocardium was 75 +/- 5 and 35 +/- 5% in the LV and 35 +/- 7 and 20 +/- 5% in the RV, respectively. Thus, in dilated failing human hearts secondary to previous MI or DCM, MMP activity is increased. This is particularly the case within the endomyocardium of the infarcted and noninfarcted portions of either ventricle with MI and in both ventricles in DCM. This suggests that an activation of collagenase throughout the myocardium may contribute to its remodeling that includes ventricular dilatation and wall thinning.
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PMID:Matrix metalloproteinase activity expression in infarcted, noninfarcted and dilated cardiomyopathic human hearts. 871 34

Human heart matrix metalloproteinases (MMP) are present in the latent form and activated in the failing heart. To examine whether the MMP activation was due to gene and/or post-translational modification, we analysed tissue from 10 explanted hearts due to coronary heart disease (CHD) and five normal left atrial tissue from donor hearts. Based on in situ immunolabeling MMP-1, tissue inhibitor of metalloproteinase (TIMP-1) and collagen were co-localized in the interstitial tissue. Based on sandwich ELISA, TIMP-1 and MMP-1 levels were 37 +/- 8 ng/mg and 9 +/- 2 ng/mg in normal tissue (P < 0.01) and 12 +/- 5 ng/mg and 75 +/- 11 ng/mg in the infarcted tissue (P < 0.01), respectively. These levels suggest repression of TIMP-1 during myocardial infarction. Northern blot analysis indicated that the mRNAs for both MMP-1 and TIMP-1 were increased three-to four-fold in the infarcted tissue as compared to the normal tissue, suggesting upregulation of MMP and TIMP gene transcription following infarction. Based on in situ tissue overlay zymography, the generalized activation of MMP was observed in the interstitium of the infarcted heart. Zymographic and immunoblot analysis demonstrated the presence of one band at 66 kDa (MMP-2) in the normal tissue and several bands at 92 (MMP-9), 66 (MMP-2) and 54 kDa (MMP-1) in the infarcted heart. Incubation of the zymographic gel with metal chelator (phenanthroline) abolished bands at 92 kDa and 54 kDa but phenanthroline did not abolish the lytic band at 66 kDa. The 66 kDa band was completely abolished in the presence of phenanthroline and phenyl methyl sulfonyl fluoride (PMSF). 2D-zymographic analysis suggested that the lytic band at 66 kDa was a mixture of two neutral proteinases with different isoelectric point. Plasminogen/gelatin zymographic analysis of infarcted tissue extract indicated that the band at 66 kDa was plasmin generated due to increased expression of tissue plasminogen activator (tPA) activity. In relation to increased expression of gelatinase in the infarcted tissue, our data suggest that gelatinase B (92 kDa) is induced in diseased heart. The results suggest that tPA converts plasminogen to plasmin which, in turn, activates MMPs and inactivates TIMP-1 post-translationally following ischemic cardiomyopathy.
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PMID:Post-transcriptional regulation of extracellular matrix metalloproteinase in human heart end-stage failure secondary to ischemic cardiomyopathy. 884 29

Although heart attack is caused by occlusion of a major coronary artery, some patients have occlusion without heart attack because these patients have sufficient collateral circulation to provide an alternate pathway for blood supply to the myocardium at ischemic risk. The growth of new capillary vessels (angiogenesis) and enlargement of preexisting vessels play an important role in the collateral development. We evaluated the hypothesis that extracellular matrix metalloproteinase (MMP) expression is altered in coronary collateral arteries (0.5-1 mm o.d.) isolated from canine hearts 2-4 months after surgical placement of an ameroid occluder around the proximal left circumflex artery (n = 4), during the development of collateral vessels and restructuring new vessels. Histologic studies (hematoxylin and eosin, trichrome, and van Gieson stains) indicated cellular proliferation and increased collagen and elastin content in collateral vessels compared with comparable-sized unoccluded arterial segments of the left anterior descending (LAD) artery. In situ MMP activity of collateral vessels, measured using denatured collagen in the gel matrix, indicated an increase in total MMP activity in the intima of collateral vessels compared with normal LAD vessels. To further identify the type of MMP, tissue homogenates were prepared from collateral and LAD vessels and analyzed by SDS-PAGE zymography. The results suggest induction of gelatinase A and gelatinase B expression in collateral vessels compared with normal LAD tissue, when identical amounts of total protein were loaded onto each lane in the gel. Based on plasminogen-casein zymography, we observed the tissue plasminogen activator level to be increased in collateral vessels. On the basis of immunoblot and mRNA (Northern blot) analyses, we determined that the MMP-1 level was induced in collateral vessels 2 and 4 months after ameroid occlusion. In contrast with MMP-1, the level of TIMP-1 (tissue inhibitor of metelloproteinases) was decreased significantly (p < 0.001) in collateral compared with LAD vessels, suggesting a role for arterial TIMP in anti-angiogenic activity. Collectively, these results suggest that chronic occlusion of a major coronary artery induces upregulation of vascular remodeling mechanisms subserving collateral development. Increased MMP-2 activity in collaterals may be associated with decreased levels of tissue inhibitor of metalloproteinases and fibrous tissue remodeling following angiogenic and (or) adaptive responses of the myocardium to chronic ischemia.
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PMID:Temporal expression of extracellular matrix metalloproteinases and tissue plasminogen activator in the development of collateral vessels in the canine model of coronary occlusion. 896 Mar 89


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