Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We compared in vitro heparin binding activity and in vivo intravascular clearance and aortic uptake in rabbits of native, reductively methylated and heparin-complexed low density lipoprotein (LDL) in order to explore the extracellular matrix binding vs cellular metabolism of LDL. Reductively methylated LDL formed soluble and insoluble complexes with heparin which was comparable to native LDL. Reductive methylation of LDL produced only 30% reduction in aortic uptake vs 60% reduction in plasma clearance, reflecting the relatively smaller contribution of receptor-mediated pathway in aortic tissue vs whole animal. The intravascular clearance of native and heparin-complexed LDL remained essentially the same, indicating similarities in cellular metabolism of LDL in both cases. But the aortic uptake of the heparin bound LDL was 30% less than the native LDL, suggesting an inhibition in binding of heparin-complexed LDL to tissue proteoglycans. Saline extraction accounted for only part (53-66%) of the LDL preparations that were retained by the tissue while subsequent collagenase and elastase treatments extracted 3-5% and 17-22% of the materials respectively. These results favor the contribution of arterial extracellular matrix components to the retention of LDL.
Atherosclerosis 1986 Dec
PMID:Low density lipoprotein retention by aortic tissue. Contribution of extracellular matrix. 380 Oct 86

An immuno-radiometric assay (IRMA) for determination of apolipoprotein B (apo B) in arterial intima is described. Intima was dissected from aortic biopsies obtained peroperatively. The tissue was first incubated in buffer to release a 'buffer extractable' pool of apo B. A 'tightly bound' fraction was then released by incubating the tissue in collagenase for 6 h. 'Buffer extractable' and 'tightly bound' apo B were then determined with IRMA. The IRMA is an immunological method based on the primary reaction between antigen and antibody, and it was found to be reproducible and sensitive enough for determination of apo B even in small tissue samples. In aortic intimal specimens without obvious atherosclerotic lesions, total apo B content was found to be 223 +/- 213.2 micrograms/g wet weight or 30 +/- 32.8 micrograms/mm2 intimal area (mean +/- SD). The majority of the biopsies contained 100-300 micrograms/g wet weight of apo B. This concentration corresponds to approximately 25% of the serum concentration. Duplicate tissue samples were obtained from 26 patients. The 2 samples were analysed separately and there was a highly significant correlation between apo B content in the 2 biopsies (rs = +0.89). About 20% of the tissue apo B was buffer extractable, and there was a strong positive correlation between buffer extractable and tightly bound apo B (rs = +0.76). The total amount of apo B found in non-atherosclerotic intima, is considerably lower than in previous reports. This difference might at least partly be due to different quantitation techniques but may also be due to differences between autopsy material and peroperatively obtained biopsies. The lower level reported here is more in agreement with studies on the kinetics of apo B into the arterial wall, as well as reported levels of apo B in interstitial fluid and in lymph.
Atherosclerosis 1986 Dec
PMID:A new microimmunoassay for apolipoprotein B in arterial tissue. Studies on peroperative human biopsies. 380 Oct 89

With an increasing interest in the role of the monocyte-macrophage in the pathogenesis of atherosclerosis and as a progenitor of plaque intimal foam cells, a model for the study of foam-cell differentiation in an extravascular environment has been developed. Granulomas were induced in 25 normocholesterolemic (NC) and 28 hypercholesterolemic (HC) rabbits by the subcutaneous injection of 15 ml of 1% carrageenan. Granuloma tissue was harvested at 4, 7, 14, and 28 days and studied by light and transmission electron microscopy. Macrophages and foam cells were isolated by enzymic dispersion with collagenase and cultured for further characterization by scanning electron microscopy, nonspecific esterase (NSE), and oil red O (ORO) staining. Granuloma macrophages from NC rabbits were consistently ORO-negative, contrasting with those from HC rabbits which were strongly ORO-positive, even at 4 and 7 days. With an increasing duration of exposure to hypercholesterolemia, macrophages accumulated increasing amounts of stainable lipid, and in the 28-day HC granulomas, large foam cells distended by lipid inclusions accounted for 70% of the cells present. This model has established that NSE-positive macrophages in HC granulomas accumulate lipid and assume the morphologic characteristics of atheromatous intimal foam cells.
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PMID:Evolution of foam cells in subcutaneous rabbit carrageenan granulomas: I. Light-microscopic and ultrastructural study. 396 33

The NaOH sonication digestion technique permits rapid isolation and exposure of intact networks of elastic fibers in vascular tissue for 3-dimensional observation with the SEM. The configuration of the network of elastic fibers within the vascular wall of large elastic arteries (aorta) is generally agreed to be a flexible framework through which smooth muscle cells and collagenous fibers are interwoven. However, the configuration of elastic fiber networks in muscular arteries, medium sized veins and smaller vessels remains unknown. When the lengthy standard biochemical elastin purification techniques were applied to vessels containing lesser amounts of elastic tissue and finer elastic fibers, the vessels were completely digested. In contrast, the digestion and sonication technique isolated and exposed intact networks of delicate elastic fibers in blood vessels which do not contain large amounts of elastic tissue. Unfixed vessels were cut into short segments, placed in 0.5 N NaOH and sonicated for 20-40 min. The specimens were rinsed in deionized distilled H2O, then autoclaved for 30 min. The tissue was rinsed a second time, fixed and processed routinely for SEM. Elastic stains and enzymatic digestion with chromatographically purified elastase and collagenase confirmed that the digestion and sonication technique produced clean, isolated networks of elastic fibers. Knowledge of the configuration of the networks of elastic fibers in different vessels enhances understanding of distensibility characteristics of individual vessels and serves as a baseline for studying alterations in the elastic framework which occur during aging and disease processes such as atherosclerosis, arterial hypertension and aneurysms.
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PMID:A rapid digestive technique to expose networks of vascular elastic fibers for SEM observation. 620 43

Cells of human aorta were isolated by dispersing the tissue with collagenase and elastase. The isolated cells were stained in suspension by the acridine orange fluorescent stain. The intensity of red fluorescence (greater than 580 nm) corresponding to the RNA content was measured in each individual cell and registered in a FACS II flow cytofluorometer. It was established that a cell population of human aorta is heterogenous with respect to RNA content. In a population of isolated cells, one can distinguish two subpopulations: (A) small cells with low RNA content, and (B) large cells with high RNA content. The ratio of both cell types varies in intima and media, and different types of atherosclerotic lesions. The share of cells belonging to subpopulation A is lower in media compared to intima. In intima, the number of these cells grows with the degree of atherosclerotic lesion. Possible reasons for the discovered metabolic heterogeneity of human aortic cells and prospects for the application of flow cytofluorometry to a research into cellular mechanisms of atherosclerosis is discussed.
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PMID:Heterogeneity of human aortic cells in regard to RNA content. 620 56

Bovine medial explants in culture synthesize a potent inhibitor of mammalian collagenase but not of bacterial collagenase. This inhibitor has been partially purified and has an apparent molecular weight of 45,000. It is a glycoprotein and is stable to heat, trypsin, acid and mercurials. Inhibitory activity is destroyed on reductive alkylation. The inhibitor interacts with collagenase and this interaction leads to the loss of enzymatic activity. This inhibitor may play a physiological role in the control of collagen degradation in blood vessels.
Atherosclerosis 1980 Jan
PMID:Purification and properties of a collagenase inhibitor from cultures of bovine aorta. 624 63

A unifying concept that excessive proliferation of cells and turnover of cellular matrix contribute significantly to the pathogenesis of several diseases, including cancer, atherosclerosis, rheumatoid arthritis, psoriasis, idiopathic pulmonary fibrosis, scleroderma and cirrhosis of the liver, is presented. As corollaries to this concept, the following topics are considered: (1) the role of polypeptide hormones and hormone-like mediators in the initiation, promotion and maintenance of proliferative responses; (2) alterations in collagen metabolism and collagenase activity; (3) the role of proteinases; (4) the potential use of inhibitors of proteinases for prevention of disease; and (5) the potential use of inhibitors of proliferative polypeptide hormones for prevention of disease. As specific proteolytic and proliferative biochemical mechanisms which contribute to the pathogenesis of disease become identified, there is a unique opportunity to develop new pharmacologic methods of prevention.
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PMID:Proliferative diseases. 626 92

Electrophorus electricus acetylcholinesterase is a large polymorphic enzyme. Its native forms 18 S, 14 S and 8.5 S possess a tail having a collagen-like structure. It was suggested that this tail is involved in the anchorage of the enzyme at the terminal of the synapse. Watkins et al. [1] showed that all forms of the enzyme having a collagen segment also bind to sphingomyelin liposomes with almost no binding to phosphatidylcholine (PC) liposomes. In agreement with the above results, the binding of acetylcholinesterase reported here was independent of the following liposomal parameters (a) curvature, (b) the physical state of the bilayer, (c) the gel to liquid crystalline phase transition of sphingomyelin, (d) stereospecificity of the sphingomyelin, (e) acyl chain of the sphingomyelin. The binding was reduced with increasing PC content in sphingomyelin vesicles. The binding has no effect on the bilayer integrity. The enzymatic activity can be released from the vesicles by incubation with collagenase. The association of the enzyme with the liposomes had minimal effect on its kinetic parameters (Km, Vmax). The only detectable effect was increasing enzyme stability at low enzyme concentration. This suggested that the binding of the enzyme to sphingomyelin liposomes reduced its surface denaturation. Such association was not unique to acetylcholinesterase since collagen showed similar behavior. Collagen binding to sphingomyelin liposomes was 5-10-times larger than to PC liposomes. The exact details of the interaction of collagen and collagen-like peptides with sphingomyelin bilayers are yet unknown although it differs from the well documented hydrophobic or electrostatic interactions [7]. This work proposes hydrogen bonding as a third mechanism which involves the interface region of sphingolipids molecules and the collagen or collagen-like tail of acetylcholinesterase. This binding is also of interest due to its correlation to the accumulation of sphingomyelin and collagen during aging and the development of atherosclerosis in blood vessels of mammals.
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PMID:Characterization of the association of Electrophorus electricus acetylcholinesterase with sphingomyelin liposomes. Relevance to collagen-sphingomyelin interactions. 649 89


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