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)

Cells from aortas of newborn and adult rabbits were liberated by digestion with trypsin and collagenase. More than 90% of them were viable at the end isolation. Isolated cells were used for electron microscopic examination. In the material obtained from aortas of newborn rabbits endothelial cells, fibroblasts and smooth muscle cells were present. In material from adult rabbits two kinds of endothelial cells, fibroblasts, several varieties of myocytes, fat-laden macrophages and typical foam cells were found. Various forms of myocytes seem to represent different functional stages or specialized kinds of these cells. The presence of fat laden macrophages and foam cells in the aortas of healthy adult rabbits may support the view that these cellular changes so far considered as typical of atherosclerosis are common and may be treated as an exponent of natural process of aging of vascular wall.
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PMID:Electron microscopic studies on cells isolated from aorta of newborn and adult rabbits. 122 11

Cells from aortas of healthy newborn and adult rabbits were liberated by digestion with trypsin and collagenase. In the same way were obtained free cells from the aortas of rabbits with far advanced experimental atherosclerosis. More than 90 p. 100 of the cells from all groups were viable. Isolated cells were used for electron microscopic examination. In material obtained from aortas of newborn rabbits, endothelial cells, fibroblasts and smooths muscle cells were present. In adult rabbits two kinds of endothelial cells, fibroblasts, several varieties of myocytes and foam cells were found. The bulk of aortic cells isolated from rabbits with experimental atherosclerosis consisted of endothelial cells and smooth myocytes. The cytoplasm of all myocytes contained lipid vacuoles. The lipid-loaded myocytes corresponded to the typical foam cells. Lipid content was relatively scanty in the endothelial cells. The presence of myocytes foam cells like in the aortas of healthy adult rabbits, identical as in material from experimental atherosclerosis, may support the view that these cellular changes so far considered as typical for atherosclerosis are common, and may be treated as an exponent of the natural process of aging of the vascular wall.
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PMID:Comparison of morphology of isolated cells obtained from aortas of normal and cholesterol fed rabbits. 123 42

External jugular veins that had been subjected to the hemodynamic stresses produced by experimental arteriovenous anastomosis developed 2% increased total protein contents and 17% increased collagen contents. When the stressed veins were homogenized and extracted with saline solutions, statistically significant increases in the saline-soluble proteins and in the saline-soluble collagen (87% and 267%, respectively) were observed. Increased amounts of low molecular weight peptides were found in the extracts. A fraction of these peptides could be degraded by Clostridium collagenase. The saline extract also contained proteins which resembled by their amino-acid composition the acidic structural proteins of the connective tissues. Additonally, in 3 dogs so tested, changes were found in the hydroxylation and glycosylation of lysine from gelatin extracts as well as in the lysine and desmosine contents of the insoluble elastin fractions. This is the first demonstration of a hemodynamically induced increase in the saline solubility of connective tissue proteins in the absence of dietary manipulations.
Atherosclerosis
PMID:Hemodynamically-induced increase in soluble collagen in the anastomosed veins of experimental arteriovenous fistulae. 126 60

The initiation of atherosclerosis may result from blood flow oscillatory shear stress in certain vascular sites (bending points, bifurcations, etc.) producing chronic minimal injury resulting in functional alteration of the arterial endothelium type I injury; experimentally, this is potentiated by atherogenic risk factors such as hypercholesterolemia, hypertension, immunocomplexes, viral infections, and tobacco smoke. Such minimal injury leads to accumulation of lipid and monocytes (macrophages), and subsequently, toxic products released by the macrophages produce damage of the intimal surface with denuding endothelium type II injury or damage, which attracts platelets; all of these cells release growth factors, prompting migration and proliferation of smooth muscle cells and producing a "fibro-intimal lesion" or the outside of the capsule of a predominant "lipid lesion." The lipid lesions surrounded by a thin capsule tend to be small and rupture easily, causing type III injury or damage; that is, they are soft and weak, contain large numbers of macrophages, which may release collagenase and elastase to form abscesses, and by their location, are under the effect of flow shear forces. After plaque disruption there is thrombus formation; when thrombi are small, they can become organized and contribute to the growth of the atherosclerotic plaque; when thrombi are large and occlusive, they lead to the acute coronary syndromes. New data suggest that, at the time of plaque disruption, certain "thrombogenic" risk factors modulate the degree of thrombogenicity and, thereby, the growth of the plaque versus the various acute coronary syndromes. Aside from the need for better understanding of the basic biology of atherogenesis, emphasis on identifying and modifying the primary atherogenic and thrombogenic risk factors should continue for primary prevention. Also, new approaches should focus on the identification, stabilization, and regression of the small "lipid plaques" prone to rupture (these are not necessarily angiographically apparent), as well as on the use of better and safer antithrombotic agents for prevention of progression.
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PMID:Clinical-pathological correlations of coronary disease progression and regression. 142 42

1. Atherosclerosis and aneurysm of the abdominal aorta are associated with thinning of the medial connective tissue. We have investigated the presence of the connective-tissue-degrading metalloproteinases in homogenates prepared from atherosclerotic, aneurysmal and control aortic media. 2. Gelatinase activity was much increased in homogenates from atherosclerotic and aneurysmal aorta [10.9 +/- 1.8 and 13.3 +/- 3.3 micrograms of gelatin hydrolysed h-1 (mg of protein)-1 respectively]. This gelatinase activity was highest at the luminal aspect of the aortic media, where the activity increased three- to five-fold after the destruction of alpha 2-macroglobulin. Zymograms demonstrated the principal gelatinase in atherosclerotic aorta to have a molecular mass of about 92 kDa, whereas in aneurysmal aorta there was a spectrum of gelatinase activity from 92 to 55 kDa. 3. Collagenase and stromelysin (proteoglycanase) could be detected by immunoblotting in homogenates of aneurysmal aorta, but rarely in atherosclerotic aorta and never in control aorta. Collagenase and stromelysin activities were low, but increased two- to three-fold after the destruction of tissue inhibitor of metalloproteinases. Collagenase and stromelysin activities were highest at the adventitial aspect of aneurysmal media. 4. The secretion of gelatinase by inflammatory cells at the intima of diseased aorta could have a pathological role in establishing atherosclerotic plaques and medial thinning. Secretion of collagenase, gelatinase and stromelysin from the adventitia could accelerate connective tissue degradation in the media of aneurysmal aorta.
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PMID:Metalloproteinases in degenerative aortic disease. 165 68

Previous studies from this laboratory have shown that pigeon embryo fibroblasts in culture, derived from embryo explants, do not express LDL receptors. In contrast, pigeon peritoneal macrophages and pigeon hepatocytes in culture express LDL receptors. The presence of an active LDL receptor pathway in pigeons has been further confirmed by in vivo studies which showed that receptor-mediated mechanisms were responsible for greater than 80 percent of whole body LDL clearance. The purpose of the present study was to determine the factors responsible for the failure of explant-derived pigeon embryo cells to express LDL receptors. To address this problem, both chicken and pigeon embryo cells were studied. Primary pigeon and chicken embryo cells isolated by collagenase digestion expressed high levels of LDL receptor activity using 125I-labelled pigeon LDL as the ligand. Cells isolated from chicken embryo by enzyme digestion expressed an approximately 10-fold greater LDL receptor activity than cells derived from explants. Pigeon LDL and beta-VLDL, but not methyl-LDL, HDL or mammalian LDL, bound to a limited number of receptors on pigeon embryo cells with specificity and high affinity. Other properties of the pigeon LDL receptor were similar to the mammalian LDL receptor with the exception that the pigeon LDL receptor was resistant to the proteolytic enzyme, pronase. In both pigeon and chicken embryo cells LDL receptor activity was lost with subsequent passage in culture. As a result, the failure of explant derived pigeon cells to express LDL receptors appears to be the result of two factors, the use of explant rather than enzyme-isolated cells and the loss of any remaining LDL receptor activity as a result of passage in culture. Whether this difference between pigeon and mammalian cells with respect to LDL receptor activity is the result of differences in the molecular structure of the pigeon LDL receptor remains to be determined.
Atherosclerosis 1991 Nov
PMID:The method of isolation of primary cells and their subculture influences the expression of LDL receptors on pigeon and chicken embryo cells in culture. 166 57

Human aortic endothelial cells, isolated at autopsy from a 52-year-old male dying from lung cancer, were treated with simian virus 40 (SV40). One colony was isolated from the infected endothelial cell culture 4 weeks after infection. The cells expressed SV40 large T antigen and p53 protein (p53) in their nuclei but lacted the characteristics of a transformed phenotype. The cells grew well in a monolayer over the 97th passage and exhibited Factor VIII-related antigen, Ulex europaeus 1 agglutinin (UEA-1) as endothelial cell markers, and a well-developed fibronectin network. The amount of prostacyclin synthesized by the cells was less than the amount synthesized by normal aortic or umbilical cord vein endothelial cells. The cells produced relatively large amounts of procollagenase, and 12-o-tetradecanoyl-phorbol-13-acetate (TPA) augmented the ability of the cells to produce this enzyme. These immortalized human aortic endothelial cells, which have some characteristics of normal endothelial cells and, like capillary endothelial cells, have the ability to produce collagenase, will probably prove useful for studies of atherosclerosis and angiogenesis.
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PMID:Collagenase production by immortalized human aortic endothelial cells infected with simian virus 40. 167 13

Aortic elastase and aortic collagenase were assayed in 38 patients who underwent an operation for thoracic or infrarenal aneurysm or infrarenal aortic occlusive disease and in 15 control patients (heart or kidney donors). Elastase was elevated in normal aortas of the infrarenal region (1.10 milliunits per gram, p less than 0.05), and in atherosclerotic descendens aneurysms (1.24 milliunits per gram, p less than 0.05), compared with the ascending aorta, when normal; aneurysmatic specimens revealed similar low elastolytic activities (0.10 milliunits per gram). The highest elastase content was found in infrarenal aneurysms (4.65 milliunits per gram). Collagenase assays yielded no significant differences, although higher activities were extracted from aortas of the infrarenal region. Coexistent atherosclerosis and wall destruction were evaluated by macroscopic and histologic investigation. All infrarenal specimens demonstrated severe atherosclerotic wall degeneration with depletion of elastic fibers. As the atherosclerotic specimens did not differ from normal aortas by protease assay, the higher elastase of infrarenal samples compared with the thoracic aorta suggests a more rapid fiber metabolism in the infrarenal region. The significantly elevated elastolytic activity of infrarenal aneurysms points to the decisive role of elastase in infrarenal aneurysm formation.
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PMID:Relationship between proteolytic enzymes and atherosclerosis in aortic aneurysms. 185 35

The Watanabe heritable hyperlipidemic (WHHL) rabbit reproduces human familial hypercholesterolemia due to a congenital low-density lipoprotein receptor deficiency and is characterized by elevated serum LDL cholesterol levels and early atherosclerosis. We attempted to transplant normal allogeneic hepatocytes into WHHL rabbits without chronic immunosuppression to cure the LDL receptor-deficient state. Livers from normal New Zealand White (NZW) rabbits were digested by intraportal perfusion of collagenase solution. Pure hepatocytes (PH) were obtained by Percoll gradient separation and nonparenchymal (NP) liver cells by pronase digestion. PH and NP were incubated with fluorescein isothiocyanate-monoclonal anti-rabbit class I, anti-class II, and anti-T cell antibodies and subjected to flow cytometry analysis. PH and NP were also used as stimulators in one way mixed lymphocyte-hepatocyte cultures (MLHC), before and after ultraviolet B light (UVB) exposure. Intraportal and intrasplenic injection of allogeneic PH were also performed in homozygous WHHL rabbits. PH were attached to collagen-coated dextran microcarriers (mc-PH) for intraperitoneal injection. Recipient control and transplanted WHHL rabbits received a single dose of cyclosporine subcutaneously (10 mg/kg/s.c.) at the time of transplantation. PH were mainly class I-positive (77.6%) and class II-negative (5.9%), while 31.5% of NP cells were class II-positive. In MLHC, PH did not stimulate proliferation, (stimulation index: 0.97 +/- 0.21), unlike NP (SI: 23.7). This latter response was abrogated by prior exposure of NP to UVB light. Intraportal injection of PH (n = 4) reduced serum LDL cholesterol to 60% of baseline, an effect lasting 2-3 weeks, and dose-dependent. Intraperitoneal mc-PH, 4 x 10(8) (n = 4), reduced serum LDL cholesterol levels to 45% of baseline more than 4 weeks posttransplant (P = 0.04). We conclude that transplantation of normal allogeneic NZW rabbit mc-PH reduces serum LDL cholesterol levels in homozygous WHHL rabbits without chronic immunosuppression. Longitudinal studies will establish if less atherosclerosis develops in mc-PH WHHL recipients than sham controls.
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PMID:Hepatocyte transplantation for the low-density lipoprotein receptor-deficient state. A study in the Watanabe rabbit. 214 23

Thirty human aortas with varying degrees of atheroma graded macroscopically according to the WHO classification were taken at autopsy from subjects of different ages (24-86 years). Study by light microscopy showed aortas with an intact wall (4 subjects, 25-46 years) with a thin intima and regular elastic layers, and aortas with varying degrees of modification of the wall, where the intima was of varying thickness and the elastic fibers showed varying degrees of damage (moderate lesions: 5 subjects, 35-52 yrs; severe lesions: 21 subjects, 26-86 yrs). From each aorta, a 4-cm segment from the tunica media, free of atheromatous lesions, was defatted and subjected to successive treatment with EDTA-Tris, 6 M guanidine-HCl-Tris, 6 M guanidine-HCl-Tris-DTE and collagenase. The residues (EP residues) were subjected to amino acid (AA) analysis and transmission electron microscopy (TEM) study. In the young subject, the AA composition was similar to that of elastin and the TEM images were characteristic of this substance. In the aging subject, an increase in polar AA and a parallel decrease in apolar AA and crosslinks was noted. By TEM, the elastin was seen to be associated with abundant fibrillar material. Trypsin treatment of EP residues gave E residues, whose composition and TEM appearance were similar in all samples, corresponding to the standard composition of elastin and its classic appearance by electron microscopy. We suggest that the fibrillar material removed by trypsin is the morphological reflection of the chemical variations observed in the EP residues. These correspond to contamination of the elastin by a polar protein fraction. This contamination is closely correlated with age but not with the degree of atheroma. Thus the age-related chemical changes in elastin appear to be independent of the onset and evolution of atheromatous lesions. The 10-15 nm diameter of the contaminating fibrillar material suggests that may be the microfibrillar fraction of elastic tissue.
Atherosclerosis 1990 Jan
PMID:Age-related changes in the elastic tissue of the human thoracic aorta. 217 15


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