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)

Isolated smooth muscle cells from the adult pig and rabbit aorta in primary culture undergo a spontaneous change in phenotype from a contractile to a synthetic state over 6-8 days, losing their capacity to contract and gaining the capacity to divide. The change in smooth muscle phenotype to the synthetic state is accompanied by distinct changes in the cells' ability to metabolize LDL, with the rate of degradation of 125I-labelled LDL decreasing to about one fifth of the level in contractile state cells. This does not appear to be due to changes in the number or affinity of LDL receptors since saturable binding of LDL is unaltered. The specific activities of the lysosomal enzymes acid phosphatase and N-acetyl-beta-glucosaminidase increase with change to the synthetic state as do cytochrome c oxidase (mitochondria) and NADPH-dependent cytochrome c reductase (endoplasmic reticulum). In contrast there is a slight but not significant decrease in the specific activity of the lysosomal enzyme acid cholesteryl esterase of rabbit smooth muscle cells and a significant decrease in the activity of pig cells with change in phenotype to the synthetic state. Significantly more [3H]cholesteryl oleate is recovered in synthetic state than in contractile state cells following incubation with 20 micrograms/ml unlabelled LDL and [3H]sodium oleate. Morphologically there is no difference in the number of lipid droplets in contractile and synthetic state cells after incubation in 5% normolipemic serum, but in cells grown in 10% hyperlipemic serum for 4 days synthetic state cells become almost completely filled with lipid droplets while contractile state cells are unaffected. Lipid accumulation also occurs selectively in vivo in synthetic as compared with contractile state smooth muscle cells within intimal fibromuscular thickenings induced by de-endothelialization of the carotid artery of cholesterol-fed rabbits. We suggest that accumulation of lipid in smooth muscle cells of atherosclerotic plaques is related to reduced catabolism of LDL following smooth muscle phenotypic change from the contractile to synthetic state.
Atherosclerosis 1983 Jun
PMID:Lipid accumulation in arterial smooth muscle cells. Influence of phenotype. 688 1

Arteriosclerotic lesions were formed in rat aorta by the administration of vitamin D2, a high-fat diet and a thyroid suppressing agent. This treatment increased the serum total cholesterol level to 12 times the control level. In the arteriosclerotic lesions that were induced the activities of lysosomal enzymes, such as acid phosphatase and acid lipase, were higher than in controls, that of acid cholesterol esterase was decreased, those of microsomal lipid-synthesizing enzymes--such as acyl-CoA synthetase and cholesterol ester synthesizing activity--were increased and that of neutral cholesterol esterase was decreased. These data suggest that lipid metabolism in arteriosclerotic lesions was changed, resulting in the accumulation of cholesterol esters in the aorta. Administration of high-fat diet and thyroid suppressing agent also increased the serum cholesterol levels to 12-fold the control level, but did not induce arteriosclerotic lesions. After this treatment the activities of hydrolyzing enzymes, such as acid and neutral cholesterol esterase and lipase, in the aorta increased, but the activities of lipid synthesizing enzymes also increased. These data suggest that lipid metabolism in the aorta in this condition changed to compensate for the large influx of serum lipids and to prevent arteriosclerosis. The roles of the serum lipid level, cell injury and lipid metabolism in the aorta in forming arteriosclerotic lesions are discussed on the basis of these results.
Atherosclerosis 1982 May
PMID:Lipid metabolism in arteriosclerotic arterial wall of rats. 709 82

Cultured smooth muscle cells from pig aortas were incubated with low density lipoproteins (LDL) and chloroquine for up to 5 days, as an in vitro model for lipid accumulation in atherosclerosis. Cells incubated with LDL alone had a normal morphology, except that some cells contained large lipid droplets. The activities of acid phosphatase, catalase and malate dehydrogenase were increased in homogenates prepared from these cells. Cells incubated with chloroquine alone developed large autophagic vacuoles. The activities of the three acid hydrolases, acid phosphatase, N-acetyl-beta-glucosaminidase and beta-glucuronidase, were decreased, as was the proteolytic activity of the cell homogenates at acid pH toward 125I-labelled LDL. There was, however, a transient increase in the activity of malate dehydrogenase. Chloroquine by itself was toxic to the cells, but LDL protected against this toxic effect. Cells incubated with LDL and chloroquine together developed both autophagic vacuoles and large lipid droplets. The cholesteryl ester content of the cells was increased many-fold and the non-esterified cholesterol content was increased to a lesser extent. The above four acid hydrolase activities were decreased, as was the activity of catalase, whereas the activities of lactate dehydrogenase and malate dehydrogenase were increased.
Atherosclerosis 1982 Sep
PMID:Lipid accumulation in arterial smooth muscle cells in culture. Morphological and biochemical changes caused by low density lipoproteins and chloroquine. 715 Mar 93

The characteristics and properties of lipid metabolism in the aorta and the brain microvessels of rabbits were investigated to clarify the role of lipid metabolism in formation of atherosclerosis. In rabbit aorta, cholesterol esterase and lipase each had an acidic and a neutral optimum pH, whereas acyl-CoA synthetase, acyl-CoA: cholesterol acyltransferase, triglyceride synthesizing activity and choline phosphotransferase each had one neutral optimum pH. These pH optima were similar to those in rats. High cholesterol diet induced atheromatous lesions in the aorta, but not in the brain microvessels. In atheromatous aorta, the acid lipase and acid phosphatase activities were higher than in controls, but not the acid cholesterol esterase activity. Moreover the activities of neutral lipase, acyl-CoA synthetase, acyl-CoA:cholesterol acyltransferase, triglyceride synthesis and choline phosphotransferase were increased, but neutral cholesterol esterase activity was normal. These data suggest that lipis metabolism in the atheromatous aorta is changed in a manner favoring accumulation of lipids, especially cholesterol esters. In controls, most of the above enzyme activities in the brain microvessels were higher than those in the aorta. However, these enzyme activities in the brain microvessels were not changed by cholesterol feeding. Thus it is suggested that the properties of lipid metabolism in the aorta and brain microvessels, including permeability of lipoproteins into the vessel walls, are important in formation of atherosclerosis in addition to the serum factors.
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PMID:Lipid metabolism in the aorta and the brain microvessels of rabbits on high cholesterol diet. 718 94

The effect of CH-123 (3-carbethoxy-6-methyl-1-9-(carboxy-methyl)-1-4-oxo-6,7,8,9-tetrahydro-4H-pyrid o(1,2a)pyrimidine) was investigated on the activity of 4 lysosomal enzymes: beta-glucuronidase, beta-galactosidase, N-acetyl-beta-glucosaminidase and acid phosphatase obtained from aortic smooth muscle and liver cells of rabbits. Animals were fed on a 2% cholesterol diet for 4 weeks and used an experimental atherosclerotic group. In drug-treated groups, after 4 weeks of cholesterol feeding the diet was changed to regular food and the animals were treated daily either with 50 mg/kg CH-123 or with 250 mg/kg Clofibrate. The postnuclear supernatant of homogenates of liver and aortic cells was isolated, lysosomes were fractionated by sucrose density gradient centrifugation, and the activity of enzymes was measured. In cholesterol-fed animals the enzyme activities of aorta and liver was 3-5 times higher than in the control, i.e. in the group of rabbits fed regular food. On Clofibrate treatment the enzyme activities were 2-3 times higher, but on treatment with CH-123, they were only 1.2-1.8 times above the control. Experiments suggest that CH-123 treatment suppresses the elevated lysosomal marker enzyme activities in aortic and liver cells of atherosclerotic animals.
Atherosclerosis 1981 May
PMID:Effect of CH-1243, a pyrido (1,2-a) pyrimidine derivative on the elevated activity of lysosomal enzymes of rabbit aorta and liver in experimental atherosclerosis. 724 98

In spontaneously hypertensive rats, prolonged hypertension caused a decrease in aortic cholesterol esterase activity with N-acetyl-beta-D-glucosaminidase activity increased and acid phosphatase activity unchanged [3]. The present study was undertaken to compare these changes with those caused by other experimentally induced types of hypertension. Treatment with DOCA-salt for one month significantly elevated both aortic cholesterol esterase and acid phosphatase activities. In contrast, to spontaneous hypertension, venous changes were also observed. An intake of 1% NaCl ad libitum produced results similar to those with the DOCA-salt treatment, despite the fact that blood pressure did not increase. This suggested that humoral factors were the main cause of the elevated enzyme activities in DOCA-salt hypertension. In rats made hypertensive by unilateral renal arterial constriction with contralateral nephrectomy (one clip--one kidney hypertension) or without contralateral nephrectomy (one clip--two kidney hypertension), aortic cholesterol esterase activities were unchanged, while aortic N-acetyl-beta-D-glucosaminidase, and aortic and venous acid phosphatase activities were increased. These results show distinct differences in the response of lysosomal enzymes during the three hypertensive states.
Atherosclerosis 1981 Jul
PMID:Aortic cholesterol esterase and other lysosomal enzyme activities in DOCA-salt, renal and spontaneous hypertension in the rat. 725 25

In an attempt to obtain information about the arterial lysosomal enzymes in hypertension, we biochemically investigated acid phosphatase (Ac-Pase) activity in the aorta of spontaneously hypertensive rats (SHR) and the effects of various antihypertensive drugs. Ac-Pase activity in SHR was always higher than that in age-matched control rats. The enzyme activity tended to increase progressively with advancing age, a tendency which was more pronounced in SHR than in control rats. The aging process expressed by the Ac-Pase activity seems to be accelerated under hypertensive conditions. Antihypertensive drugs such as reserpine, hydrochlorothiazide, hydralazine and propranolol significantly suppressed the rise of blood pressure and decreased the aortic Ac-Pase activity in SHR. In particular reserpine and propranolol lowered Ac-Pase activity more effectively than it did blood pressure. Hypertension as well as catecholamine seem to be involved in the increase in the aortic lysosomal enzyme activity in SHR.
Atherosclerosis 1981 Oct
PMID:Acid phosphatase activity in the aorta of spontaneously hypertensive rats and the effect of various antihypertensive drugs. 730 56

In a previous study using the J774 macrophage foam cells, we quantitated the accumulation of unesterified (free) cholesterol derived from cholesteryl ester hydrolysis in lysosomes, after phagocytic uptake of cholesteryl ester droplets. In the present study, we examined whether the accumulation of free cholesterol in lysosomes leads to the formation of cholesterol monohydrate crystals by analyzing the lipid composition of low density lysosome fractions isolated from cholesteryl ester-loaded macrophages after a 24-h incubation. Phase diagrams of the constituent lipids in the lipid-filled lysosomes predicted the formation of cholesterol monohydrate crystals. The formation of cholesterol monohydrate crystals was observed in cholesteryl ester-loaded macrophages after a 48-h incubation by polarizing light microscopy. The crystals had a density of 1.04 g/ml and the morphology of cholesterol monohydrate crystals with an acute edge angle of about 80 degrees. The crystals appeared as needles as well as plates and melted only when heated to greater than 85 degrees C. The physical properties of these crystals are characteristic of cholesterol monohydrate. In our studies, crystal formation was observed even when cells had active acyl-CoA:cholesterol acyltransferase or when cholesterol efflux was stimulated. Electron microscopy and acid phosphatase cytochemistry of lysosomes in cholesteryl ester-loaded cells confirmed that cholesterol crystal formation occurred within lipid-loaded lysosomes. Time-lapse video microscopic studies revealed that most of the cells containing cholesterol monohydrate crystals not only remain viable but also have the capacity to translocate single crystals within cells. The data demonstrate that lysosomal accumulation of free cholesterol in macrophages after phagocytic uptake and hydrolysis of cholesteryl ester droplets leads to the formation of cholesterol monohydrate crystals within lipid-filled lysosomes. Such a process may lead to deposition of free cholesterol and cholesterol monohydrate crystals in macrophage foam cells during the progression of atherosclerosis.
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PMID:Formation of cholesterol monohydrate crystals in macrophage-derived foam cells. 813 26

Ten asthmatics in remission and aggravation of the disease were examined for: lipoprotein pre-beta, beta and alpha fractions, total cholesterol and its fractions in atherogenic and antiatherogenic lipoproteins with estimation of the atherogenicity coefficient, activity of 5-nucleotide hydrolase, acid phosphatase, gamma-glutamyl transpeptidase and alcohol dehydrogenase. The results were indicative of more active atherosclerotic process in the presence of blockade which changed the activity of hepatocyte membrane lipoprotein receptors, of simultaneous operation in bronchial asthma patients of infiltrative and cellular mechanisms of atherosclerosis.
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PMID:[Atherogenesis in bronchial asthma patients: its relationship to the pathogenetic characteristics of the disease and to liver function (the clinico-biochemical aspects)]. 814 74

Human aorta was studied at early stages of atherosclerosis: intimal edema, first signs of lipoidosis, lipid spots and lipid plaques. Adhesion of Mn/Mp and lymphocytes to the aortal intima directly correlated with lipid deposits in the vascular wall. The number of mononuclear cells in the intima increased in parallel to progression of lipidosis. T-lymphocyte adhesion passed ahead of that of Mn/Mp. Cytotoxic suppressors dominated among T-lymphocytes adhered to the intima surface. Mn/Mp do not contain enzymes participating in the lipid utilization (acid lipase, acid phosphatase, nonspecific esterase) at initial stages of atherosclerosis. The activity of these enzymes starts to appear in parallel to atherosclerosis progression. HLA-DR antigen is found on the surface of T-lymphocytes and Mn/Mp indicating increased immunity of these cells.
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PMID:[Subpopulations of lymphocytes and monocytes/macrophages at the early stages of human aorta atherosclerosis]. 852 61


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