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)

Some important enzymes concerned with the biosynthesis of the precursors of glycosaminoglycans (gg), degradation of gg and biological sulphation have been studied in rats fed an atherogenic diet. L-Glutamine-D-fructose-6-phosphate amino-transferase and glucosamine-6-phosphate-N-acetylase--2 enzymes concerned with the biosynthesis of hexosamine precursors of gg--decreased in the liver in rats fed the atherogenic diet. UDPG pyrophosphorylase, UDPG dehydrogenase and UDPG glucuronic acid-5'-epimerase, which are concerned with the biosynthesis of the uronic precursors of gg, also decreased in the liver in the diet-fed rats. The activities of some of the enzymes concerned with degradation of gg-hyaluronidase, beta-glucuronidase beta-hexosaminidase, cathepsin and aryl sulphatase--increased both in the liver and aorta. The hepatic concentration of PAPS significantly decreased in the diet-fed rats. The sulphate-activating system, which includes ATP sulphurylase, APS kinase and sulphotransferase, also decreased. Thus the overall picture is one of decreased synthesis of gg and their increased degradation in the atheromatous rats.
Atherosclerosis
PMID:Metabolism of glycosaminoglycans in atheromatous rats. Enzymes concerned with synthesis, degradation and sulphation of glycosaminoglycans. 12 76

The effect of low and high doses of ascorbic acid on glycosaminoglycan and lipid metabolism was studied in guinea pigs fed both normal and atherogenic diets. The high dose of ascorbic acid (25 mg/100 g body weight/day) decreased the cholesterol level in the liver and aorta but not in the serum in animals fed the normal diet in comparison with those fed the low dose of ascorbic acid (0.1 mg/100 g body weight/day). In animals fed the atherogenic diet, cholesterol decreased in the serum and liver, but not in the aorta. Serum triglycerides were not affected by the dose of ascorbic acid in the group on the normal diet, but in the animals receiving the atherogenic diet, the high dose of ascorbic acid caused serum triglycerides to decrease when compared with the low dose. Hepatic and aortic triglycerides decreased in groups on normal and atherogenic diets receiving the high dose of ascorbic acid. Lipoprotein lipase activity was not affected in the aorta by the dose of ascorbic acid either in the normal or atherogenic diet group. It was increased in the liver and heart in both the groups receiving the low dose of ascorbic acid but decreased in the high dose group. The concentration of all the glycosaminoglycans significantly increased in the aorta of animals on normal diet receiving the high dose of ascorbic acid when compared with the low dose group. In the group on the atherogenic diet, hyaluronic acid was not affected, but all the sulphated glycosaminoglycans increased in the animals receiving the high dose when compared with those receiving the low dose. In the liver all the sulphated glycosaminoglycans increased while hyaluronic acid decreased in both the normal and atherogenic diet groups receiving the high rather than the low dose of ascorbic acid. L-Glutamine:D-fructose-6-phosphate aminotransferase and UDPG dehydrogenase, two key enzymes in the biosynthesis of precursors of glycosaminoglycans, were studied in relation to the dose of ascorbic acid. Hepatic aminotransferase activity was higher both in the normal and atherogenic diet groups when receiving the high rather than the low dose of ascorbic acid. UDPG dehydrogenase was not affected by the dose of ascorbic acid. The activities of the degrading enzymes -- hyaluronidase, beta-glucuronidase, beta-hexosaminidase and aryl sulphatase -- significantly increased both in the normal and atherogenic diet groups when receiving the low rather than the high dose of ascorbic acid. The concentration of PAPS, sulphate activity and sulphotransferase activity were all increased in both the normal and atherogenic diet groups receiving the high dose of ascorbic acid.
Atherosclerosis
PMID:Ascorbic acid and glycosaminoglycan and lipid metabolism in guinea pigs fed normal and atherogenic diets. 12 67

The changes in levels of glycosaminoglycans (GAGs) of the intima and media of the human artery in atherosclerosis were determined by a recently introduced two-dimensional electrophoresis technique that permits direct measurments of each of these macromolecules. To identify the arterial GAGs, they were fractionated by chromatography on a DEAE-Sephadex A-25 column, and the resulting three fractions (hyaluronic acid [HA], heparan sulfate [HS], and the partially separated chondroitin sulfates B [CSB] and C [CSC]) were analyzed for their electrophoretic mobilities by this electrophoretic method, for their digestability by highly specific hydrolases (leech hyaluronidase, heparinase, and chondroitinases ABC and AC) and for their iduronic acid content. From these studies we concluded that normal and atherosclerotic human aortas contain CSB, CSC, HA, and HS. Further, we demonstrated that CSB is a hybrid consisting of approximately 40% CSA and 60% CSB and that CSC appears to be a polymer consisting essentially of glucuronic acid and N-acetylgalactosamine-6-sulfate. Classical CSA as well as chondroitin (CH) were not present in detectable amounts. In the relatively normal intima, the mean concentrations of the GAGs were found to be 4.7, 20.9, 1.3, and 5.1 mg/g of dry, defatted, decalcified tissue for CSB, CSC, HA, and HS, respectively. With the progression of atherosclerosis, there was a pronounced decrease in the total GAG content (from 32 to 18 mg) associated with a decrease in the CSC and HS levels but without a change in the HA concentrations. Of particular interest, however, was the increase in the CSB level. In the media whose total GAG content averaged approximately 20 mg, no significant changes in these GAG levels were noted with the progression of the disease except for that of CSC. These findings may be important in explaining the increased lipoprotein and collagen deposition in the diseased aorta.
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PMID:The glycosaminoglycans of the human artery and their changes in atherosclerosis. 13 44

An hypothesis is proposed that atheroma may be classified as a leiomyosarcoma derived from the tunica media of an artery. The notion that atheroma is a neoplastic disease provides a simple explanation for a highly complex phenomenon; the pathogenesis of artherosclerosis. According to this hypothesis some smooth-muscle cells in the media undergo malignant transformation, which is manifested by excessive production of hyaluronidase and other glycosaminoglycan hydrolases. This enzymic system frees cells from their bonds and allows them to proliferate. The enzymes also evoke a fibroblast hyperplasia which is followed by a protective collagenization producing a local area of increased resistance to the hydrolases. This accounts for the sclerosing aspect of the disease. Several other features of atherosclerosis are a result of the neoplastic nature of the disease.
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PMID:Atheroma as a neoplastic disease. 90 1

Aortic tissues consisting of all three tunics were removed from normal adult rabbits and cultured in a semisynthetic gelosed medium supplemented by 10% serum obtained either from normal or hypercholesterolemic rabbits. Fibrillar cross-striated aggregates appeared with a high frequency (50%) in the extracellular space of explants cultured from four to eight days in medium supplemented by serum from hypercholesterolemic rabbits, but did not appear in explants cultured in serum from control animals (3%). The electron-dense segment was ruthenium red positive and digested by testicular hyaluronidase. The electron-lucent segment, composed of ruthenium red negative thin filaments, was not modified after hyaluronidase treatment but was strongly digested after collagenase treatment. It is believed that this material was fibrous long spacing collagen synthetized under culture conditions, as shown after tritiated proline incorporation.
Atherosclerosis 1977 Sep
PMID:Fibrous long spacing collagen in aortic explants of normal rabbit cultured in hypercholesterolemic serum. 91 68

Prolonged exposure of rats to cigarette smoke resulted in significant alteration in the metabolism of glycosaminoglycans (GAG) and glycoproteins (GP). The concentration of many GAG fractions generally decreased in the aorta, liver and heart, but increased in the lungs. Concentration of chondroitin sulphates decreased in all the tissues. The activity of many enzymes concerned with the degradation of GAG (hyaluronidase, beta-glucuronidase and cathepsin-D) showed increase in these tissues. The concentration of the carbohydrate components (total hexose fucose and sialic acid) of aorta, heart and liver showed decrease in the rats exposed to cigarette smoke while there was increase in the lungs. The activity of many glycohydrolases generally showed increase in these tissues. Thus, exposure of rats to cigarette smoke for long periods produced changes in the aortic GAG and GP which are similar to those observed in atherosclerosis. On the other hand there was accumulation of many GAG in the lung tissue.
Atherosclerosis 1991 Jan
PMID:Changes in the glycosaminoglycans and glycoproteins in the tissues in rats exposed to cigarette smoke. 206 35

Aortic glycosaminoglycans were separated into fractions of increasing molecular weights containing heparan sulfate or chondroitin 4/6-sulfate + dermatan sulfate. When these fractions were added to plasma low density lipoproteins (LDL) in the presence of Ca2+, only chondroitin 4/6 sulfate + dermatan sulfate of high relative molecular weight produced turbidity. Treatment with testicular hyaluronidase abolished totally the formation of insoluble complex. When these glycosaminoglycans were applied to LDL-affinity columns in the presence of Ca2+, higher NaCl concentrations were necessary for the elution of the high relative molecular weight chondroitin sulfate. Heparan sulfate fractions did not produce turbidity when added to LDL solutions and were eluted from LDL-affinity columns at low NaCl concentrations. All these results suggest that besides the structure (or charge density), the molecular weight of the chondroitin sulfate chains is a relevant factor for the binding of this compound to LDL.
Atherosclerosis 1988 Oct
PMID:Interaction of high molecular weight chondroitin sulfate from human aorta with plasma low density lipoproteins. 314 91

The interaction of glycosaminoglycans and proteoglycans with low density lipoproteins has been studied. Aortic and cartilaginous glycosaminoglycans are retained in LDL affinity columns and produce turbidity when added to LDL in presence of Ca2+. When extracted from whole aortic walls, dermatan sulfate is the glycosaminoglycan that shows greatest affinity for LDL. However, when using the glycosaminoglycans obtained by papain hydrolysis of the proteoglycans extracted from aorta, the binding affinity with LDL was similar for dermatan sulfate and chondroitin 4/6-sulfate. Removal of the protein core of the aortic or cartilaginous proteoglycans did not prevent interaction with LDL. However, treatment with testicular hyaluronidase abolished totally such interaction. When aortic glycosaminoglycans and proteoglycans were applied to LDL affinity columns in presence of Ca2+, a marked increase in the average molecular weight of the glycans found in the eluates of higher NaCl concentration was observed. This result suggests that the molecular weight of the glycosaminoglycans is a relevant factor for the binding of these compounds to LDL.
Atherosclerosis 1984 Feb
PMID:The binding of human aortic glycosaminoglycans and proteoglycans to plasma low density lipoproteins. 671 67

The activity of lysosomal hydrolases (hyaluronidase and beta-glucuronidase) as well as elastolytic activity in arterial wall and blood serum of rats with experimental atherosclerosis were determined. An increase of the enzyme activity was found in arterial wall, while in blood serum the rise of lysosomal hydrolase activity was accompanied by and unchanged level of elastolytic activity, as compared to control animals. The present studies show the participation of lysosomal enzymes and elastolytic activity in the development of atherosclerotic changes.
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PMID:Activity of selected enzymes in arterial wall and blood serum of rats with experimental atherosclerosis. 691 90

The acidic glycosaminoglycans (AGAG) of the human coronary arterial tree (the main left and right branches and their distal portions) were analyzed by enzymatic methods employing chondroitinases, hyaluronidase and heparitinase. The AGAG content of human coronary arteries was highest in the left branch, intermediate in the right branch and lowest in the distal portions. Some compositional differences in AGAG were found in these three parts. The amount of AGAG in the coronary arterial tree decreased with increasing severity of atherosclerosis. The main AGAG were heparan sulfate (HS) and chondroitin 6-sulfate (C-6S), constituting 33-38% and 24-36% of the total AGAG, respectively. Dermatan sulfate (DS) and chondroitin 4-sulfate (C-4S) each comprised 1/5-1/10 of the total AGAG. Hyaluronic acid (HA) and oversulfated DS comprised smaller proportions of the total AGAG. A small amount of heparin was occasionally detected in the coronary arterial tree, particularly in the distal portions. The lipid content of the main branches was increased in mildly atherosclerotic parts but diminished in severely affected parts. The water content was relatively higher in the main branches and decreased with severity of atherosclerosis. A possible function of these AGAG in atherosclerosis is discussed with respect to the compositional changes.
Atherosclerosis 1982 Oct
PMID:Acidic glycosaminoglycan, lipid and water contents in human coronary arterial branches. 715 90


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