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)

Aneurysms of the abdominal aorta occur with atherosclerosis or connective tissue disorders. Changes of three components of aortic media, smooth muscle cells, elastin, and collagen, which could contribute to medial weakening, are discussed. Smooth muscle cells cultured from the aging abdominal aorta (normal, atherosclerotic, or aneurysmal) have limited replicative potential at five to six cell doublings, whereas cells from aneurysmal thoracic aorta undergo more than 20 cell doublings in culture. The elastin content is much reduced in aneurysms and this is associated with an increase in elastase activity of medial homogenates to 17.8 U/ng of deoxyribonucleic acid (DNA) compared with 8.3 and 4.4 U/ng of DNA in atherosclerotic and normal aorta, respectively. An elastinolytic enzyme has been purified from aneurysmal aorta and appears to have different properties from human leukocyte elastase. Ruptured aneurysms are associated with an increased total collagenase activity but the increase could be stimulated by, or result from, an influx of inflammatory cells and does not necessarily have a causal significance. In patients with a family history of aneurysm there appears to be a decreased content of type III collagen in aortic media: 24% +/- 4% compared with 32% +/- 5% in most aneurysms. Familial aneurysms are most common in women, and preliminary results suggest that a polymorphic variant of the type III collagen gene, defined by restriction enzyme digest, may be associated with aneurysmal disease in women. The genetic approach may define causal mechanisms predisposing patients to aneurysmal dilatation.
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PMID:Cellular, enzymatic, and genetic factors in the pathogenesis of abdominal aortic aneurysms. 253 34

Intimal cells from human aortic fatty streak lesions were isolated with collagenase-elastase digestion and the cellular uptake of lipoproteins fluorescently labeled with 3,3'-dioctadecylindocarbocyanine (DiI) was studied in primary culture. The majority of the cells in primary culture contained lipid droplets and the foam cells consisted of both macrophages and smooth muscle cells (SMC), identified with electron microscopy and the macrophages also using the monoclonal anti-Leu-M3 antibody. The lipid inclusions contained cholesteryl ester, as visualized with filipin staining. Arterial macrophages took up DiI-labeled acetylated low density lipoprotein (DiI-acetyl-LDL) in the same way as did monocyte-macrophages isolated from blood. DiI-labeled beta-very low density lipoprotein (DiI-beta-VLDL) isolated from cholesterol-fed rabbits, was taken up by both macrophages and SMCs. In macrophages DiI-beta-VLDL was internalized also in the presence of excess unlabeled low density lipoprotein (LDL), whereas in SMCs the uptake was partially prevented. DiI-LDL uptake was only seen in SMCs free of lipid inclusions and especially during cell growth. The present results show that, in human aortic fatty streaks, (a) both macrophages and SMCs accumulate cholesteryl ester, (b) macrophage foam cells possess active scavenger receptors capable of mediating the uptake of acetyl-LDL, and (c) macrophages are also capable of accumulating cholesteryl ester by receptor-mediated uptake of beta-VLDL.
Atherosclerosis 1989 Oct
PMID:Macrophage foam cells from human aortic fatty streaks take up beta-VLDL and acetylated LDL in primary culture. 268 64

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).
Atherosclerosis 1989 Jun
PMID:Apolipoprotein B in human aortic biopsies in relation to serum lipids and lipoproteins. 278 44

The plasma clearance rate of high density lipoprotein is reduced in the hypothyroid rat. Because the liver is an important site of HDL-cholesterol catabolism, the present study was undertaken to investigate whether thyroid hormone deficiency affects binding of HDL to liver cells. Male Wistar rats were made hypothyroid by feeding propylthiouracil (0.1% w/w). Liver cells were isolated by in situ perfusion of the liver with a buffered collagenase solution. 125I-labelled rat HDL binding to isolated liver cells was carried out at low temperature on ice. For both control and hypothyroid rat liver cells, 125I-HDL binding was significantly inhibited by excess unlabelled rat HDL and also by human HDL3 and human LDL but was unaffected by the addition of 10 mM EDTA. From Scatchard analysis of dose-response studies, hypothyroid cells displayed a lower HDL binding capacity (P less than 0.01) and a higher binding affinity (P less than 0.025) compared to control cells. These results suggest that thyroid hormone affects the expression of the HDL binding site in liver cells which may contribute to the reduced HDL clearance in the hypothyroid animal.
Atherosclerosis 1989 Sep
PMID:Hypothyroidism reduces HDL binding to rat liver cells. 280 42

Primary cultures of typical and modified smooth muscle cells isolated from the intima of human aorta were used to study the mechanism whereby low density lipoprotein (LDL) induces accumulation of intracellular cholesterol. Incubation of intimal cells with native LDL obtained from human plasma did not lead to deposition of total cholesterol. LDL added to the cultures simultaneously with hyaluronic acid, heparin, chondroitin sulfate, fibronectin, and mouse monoclonal antibody against LDL also failed to alter the cellular cholesterol. On the other hand, 24-h incubation of the cells with LDL in the presence of dextran sulfate, gelatin, particles of aortic elastin, particles of collagenase-resistant aortic matrix, goat polyclonal antibodies against LDL or latex beads caused a significant (1.5-7-fold) increase in total cholesterol. The compounds which stimulated cholesterol deposition are able to form precipitating complexes with LDL. On the contrary, the agents which failed to induce cholesterol accumulation were unable to insolubilize LDL. A direct correlation (r = 0.927) was found between the cholesterol content of the insoluble complex and the increment of cholesterol in the cultured cells. To find out whether LDL plays a specific role in the deposition of intracellular cholesterol, very low density lipoproteins and high density lipoproteins were used. These lipoproteins stimulated the accumulation of intracellular cholesterol in the presence of agents capable of forming insoluble associates with them. Our data suggest that insolubilization of lipoproteins is a key event in the LDL-mediated accumulation of intracellular cholesterol induced by various agents.
Atherosclerosis 1989 Sep
PMID:Insolubilization of low density lipoprotein induces cholesterol accumulation in cultured subendothelial cells of human aorta. 280 47

Fibronectin is associated with cell attachment and migration and interacts with fibrin, collagen and glycosaminoglycans; thus, it may be a factor in the focal proliferation of smooth muscle cells and collagen in atherosclerosis. We have measured, by rocket immunoelectrophoresis, the concentrations of soluble and collagenase-releasable fibronectin in normal human aortic intima and different types of atherosclerotic lesions. Soluble fibronectin concentration showed no significant difference between normal intima and lesions, but was 6-8-times higher than expected on the basis of plasma concentration and molecular mass. The concentration free in the interstitial fluid was about 3-times the expected level, suggesting that it originates from local synthesis as well as plasma insudation. In tissue, about half the fibronectin appeared to be reversibly associated with tissue components. Incubation with collagenase released fibronectin equal to twice the soluble fraction from normal intima and early proliferative lesions. In more advanced plaques that were accumulating lipid, the amount released was significantly higher (P less than 0.05) and more than 3-times the soluble fraction, suggesting that it might be involved in lipid accumulation. However, there was no correlation between release of fibronectin and bound low-density lipoprotein.
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PMID:Fibronectin distribution in human aortic intima and atherosclerotic lesions: concentration of soluble and collagenase-releasable fractions. 300 86

Endothelial cells (EC) were harvested by 0.1% collagenase treatment for adult human thoracic aortas obtained 1-3 h after sudden death. At least 35-70% of EC were removed from the intimal surface of aorta, 90-95% of them being viable. Plating efficiency was 70-80%. Monolayer formation was achieved at a seeding density of 5-8 X 10(2) cells/mm2. The cells were identified as endothelium by the presence of Factor VIII antigen, Weigel-Palade bodies and typically endothelial morphology at confluence. Unlike endothelial cultures derived from human umbilical veins and infant aortas, primary cultures obtained from human adult aortas contain multinuclear EC with Factor VIII antigen and Weibel-Palade bodies. The number of multinuclear EC in cultures isolated from aortas affected by atherosclerosis was 2-fold higher (P less than 0.05) than in cultures obtained from grossly normal aortas taken from donors of the same age. EC with numerous lipid inclusions revealed by oil-red-O staining were present in all the EC primary cultures derived from aortas affected by atherosclerosis. No oil-red-O-positive cells were detected among the EC cultured from infant aorta, aorta of young donors, and umbilical vein. An electron microscopic examination of EC from atherosclerotic aorta in culture and in situ failed to reveal any ultrastructural peculiarities distinguishing multinuclear EC from the mononuclear EC.
Atherosclerosis 1986 Jan
PMID:Primary culture of endothelial cells from atherosclerotic human aorta. Part 1. Identification, morphological and ultrastructural characteristics of two endothelial cell subpopulations. 300 20

Subendothelial cells (SEC) were obtained from the inner intimal layer of adult human aorta by collagenase treatment. SEC were identified in primary culture either as smooth muscle cells by staining with FITC-labeled antisera against human smooth muscle myosin or as macrophages, foam cells and contaminating endothelial cells by their uptake of malondialdehyde treated low density lipoproteins labeled with fluorescent dye 3,3'-dioctadecylindocarbocyanine. Between 1 and 5 days in culture, along with smooth muscle cells (SMC, 38-82%), endothelial cells (0-9%), macrophages and foam cells (2-32%), one more type of cell was found. This cell type resembled SMC in size and shape, but was not stained by antisera to SMC myosin. By ultrastructural criteria these cells were characterized as modulated SMC for they contained prominent rough endoplastic reticulum and Golgi complex together with basement membrane and a large number of plasmalemmal vesicles. Like SMC they reacted with phalloidin and were stained by anti-vimentin but not by anti-desmin monoclonal antibodies. The proportion of such cells varied from 5 to 33% of total cell number and increased in parallel to macrophages and foam cells in vessels with well developed atherosclerotic lesions. We conclude that the applied technique may be used for identification of cultured vascular cells including modulated SMC.
Atherosclerosis 1988 May
PMID:Identification of intimal subendothelial cells from human aorta in primary culture. 313 80

To reveal the presence of atherogenic potential in the blood serum obtained from patients with angiographically assessed coronary atherosclerosis we used primary cultures of subendothelial cells isolated by collagenase from unaffected human aortic intima. Earlier, we have demonstrated that such cultures are made up mostly of typical and modified smooth muscle cells. Within 24 hours of cultivation with a 40% sera of patients suffering from coronary atherosclerosis, the total intracellular cholesterol level increased twofold to fivefold. Cultivation with the sera of healthy subjects had no effect on the intracellular cholesterol level. The sera of patients were separated by ultracentrifugation into two fractions: total lipoprotein fraction containing the main classes of lipoproteins and a lipoprotein-deficient fraction. The former, but not the lipoprotein-deficient fraction, was characterized by atherogenicity (i.e., the ability to induce the accumulation of intracellular cholesterol). Lipoproteins of the patients' serum were separated into main classes: low density lipoproteins (LDL), very low density lipoproteins (VLDL), and high density lipoproteins (HDL2 and HDL3). An atherogenic component of the serum capable of stimulating the deposition of intracellular cholesterol was represented by LDL and, in one case, by VLDL, but not by other classes of lipoproteins. LDL and other lipoproteins isolated from the blood serum of healthy subjects failed to raise the cholesterol content in cultured cells; that is, they were nonatherogenic.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blood serum atherogenicity associated with coronary atherosclerosis. Evidence for nonlipid factor providing atherogenicity of low-density lipoproteins and an approach to its elimination. 334 73

Atherosclerotic aortic intimas of cholesterol-fed rabbits were enzymatically dispersed into single cells by collagenase and elastase. And monocyte-macrophages (M phi) were separated from smooth muscle cells (SMC), using the ability of M phi to adhere to a plastic dish firmly even in the enzyme solutions. Round or oval, heavily lipid-laden cells, so-called foam cells (FC), belonged to the M phi fraction. M phi-FC showed very strong activity for non-specific esterase using alpha-naphthyl butyrate, while SMC showed little or no activity. Some of the FC were large and multinucleated (multinucleated giant foam cells). They also showed positive non-specific esterase staining and are thought to be derived from M phi. M phi-FC synthesized various proliferate in the medium and the number decreased gradually within several days. Some SMC were heavily lipid-laden; however, they retained their original spindle shape. SMC lost lipid droplets gradually as they proliferated to confluence. SMC from atherosclerotic lesions showed higher proliferative activity than those from normal-appearing medias of atherosclerotic aortas or control aortas. Almost no M phi-FC were obtained from the intima-medias of grossly normal portions of atherosclerotic aortas and control aortas. The present method will be useful for studying the role of these cells in the pathogenesis of atherosclerosis.
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PMID:Separation and characterization of macrophages and smooth muscle cells in rabbit atherosclerotic lesions. 366 43


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