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)

Copper deficiency adversely affects the extracellular matrix of the arterial wall, leading to cardiovascular lesions. To study the lesions resulting from copper deficiency, the composition of proteoglycans from aortas of copper-deficient rats was compared with proteoglycans of aortas from copper-supplemented rats. Copper deficiency in rats was verified by copper levels in adrenal glands (mean +/- SE, 0.37 +/- 0.07 vs 1.03 +/- 0.17 micrograms/g wet wt in supplemented rats). The proteoglycans were isolated from the aorta by extraction with 4 M guanidine-HCl and by digestion of the tissue with elastase. The proteoglycans were purified by CsCl isopycnic centrifugation and fractionated by gel filtration. The fractions were characterized for molecular size and glycosaminoglycan composition. Total uronate in the aortas from copper-deficient rats was 25% greater than in aortas from copper-supplemented rats, and the proteoglycans from copper-deficient rat aortas were of greater molecular size. Among the glycosaminoglycans the concentration (microgram/mg tissue) of isomeric chondroitin sulfates, particularly dermatan sulfate, was greater in copper-deficient animals than in copper-supplemented animals. These observations are similar to earlier findings in experimental atherosclerosis and to a response of cardiovascular connective tissue to injury.
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PMID:Composition of proteoglycans in the aortas of copper-deficient rats. 291 12

Dehydroepiandrosterone (DHEA) is an endogenous steroid that blocks carcinogenesis, retards aging, and exerts antiproliferative properties. In vitro, it is a potent inhibitor of glucose-6-phosphate dehydrogenase, the first committed step of the pentose phosphate pathway. In man, serum levels of DHEA and its sulfate peak in early adulthood and drop markedly with age. Epidemiologic evidence indicates that low levels of DHEA or its sulfate conjugate are linked to an increased risk of developing cancer or of death from cardiovascular disease. Like cancer, atherosclerosis is a proliferative process characterized by both initiation and promotion phases. This similarity provided a framework in which to study the antiatherogenic effects of DHEA. Rabbits were randomly assigned to four groups. Two groups of rabbits received aortic endothelial injury by balloon catheter and were fed a 2% cholesterol diet for 12 wk. DHEA, 0.5%, was incorporated into the diet of one group receiving the 2% cholesterol diet and endothelial injury and also into the diet of one of the control groups. Animals were killed after 12 wk and aortas, hearts, and livers were studied. Plasma samples were analyzed for total cholesterol, VLDL, LDL, HDL, triglycerides, DHEA, and DHEA-sulfate levels. The atherogenic insult resulted in severe atherosclerosis in animals not treated with DHEA. In those receiving DHEA there was an almost 50% reduction in plaque size (P = 0.006), inversely related to the serum level of DHEA attained. Fatty infiltration of the heart and liver were also markedly reduced. These beneficial actions were not attributable to differences in body weight gain, food intake, total plasma cholesterol or distribution of cholesterol among the VLDL, LDL, or HDL fractions. The results show that high levels of plasma DHEA inhibit the development of atherosclerosis and they provide an important experimental link to the epidemiologic studies correlating low DHEA-sulfate plasma levels with an enhanced risk of cardiovascular mortality.
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PMID:Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury. 296 22

We have raised specific antibodies against the protein component of baboon lipoprotein (a) (Lp(a]. Apolipoprotein (apo) Lp(a) is a very large protein which separates into two distinct proteins, apo B and apo (a), when 2-mercaptoethanol is included during sample treatment for sodium dodecyl sulfate-electrophoresis. The antibodies were specific for baboon apo (a) and apo B. The presence of the two distinct antigens in the lipoprotein permitted the development of an enzyme-linked immunosorbent assay that was specific for Lp(a) particles in serum. The assay could detect less than 1 ng of Lp(a) protein per well and was useful in the range of 1-9 ng. The assay was specific for Lp(a) and did not respond to other lipoproteins, such as low density lipoprotein. Lp(a) could be accurately quantitated in serum frozen at -80 degrees C in plastic tubing segments. Using the Lp(a) assay, the mean serum level of 80 unrelated baboons was 4.7 mg/dl, with the distribution skewed toward the lower levels. These data further support the value of the baboon as a model of the atherogenic lipoprotein Lp(a).
Atherosclerosis 1988 Sep
PMID:Immunochemical characterization and quantitation of lipoprotein (a) in baboons. Development of an assay depending on two antigenically distinct proteins. 297 92

A semipurified, cholesterol-free diet containing 40% carbohydrate can produce aortic sudanophilia or aortic atherosclerosis in vervet monkeys (Cercopithecus aethiops pygerethrus) depending on the particular carbohydrate fed. Four groups of vervet monkeys (three males and three females per group) were fed semipurified diets containing lactose. Two of the groups were also fed 15% cellulose (C) or 15% cellulose plus 0.1% cholesterol (CC); the two other groups were fed 15% pectin (P) or 15% pectin plus 0.1% cholesterol (PC). The average serum total cholesterol and low density lipoprotein cholesterol levels over the entire feeding period (mg/dl +/- SEM) were, for C, 156 +/- 14 and 95 +/- 5; for P, 173 +/- 15 and 112 +/- 8; for CC, 187 +/- 27 and 122 +/- 21; and for PC, 155 +/- 11 and 108 +/- 7. Cholesterol levels at autopsy (mg/dl +/- SEM) were, for C, 103 +/- 6; for P, 108 +/- 16; for CC, 92 +/- 9; and for PC, 106 +/- 7. Aortic sudanophilia (percentage of area) was, for C, 5.9 +/- 2.7; for P, 13.5 +/- 9.4; for CC, 5.3 +/- 2.1; and for PC, 21.6 +/- 10.3. Dietary pectin led to more severe sudanophilia (increased by 129% in the absence of cholesterol and by 308% in its presence) than did cellulose. Analysis of aortic glycosaminoglycans (GAG) revealed that dermatan sulfate levels fell in both cholesterol-fed groups, and chondroitin sulfate fell in aortas of group CC. Heparan sulfate levels were unaffected by cholesterol feeding. Hexuronic acid, galactosamine and hexosamine levels were elevated in the pectin-fed monkeys, but levels were unaffected by dietary cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of dietary fiber on lipids and aortic composition of vervet monkeys. 301 55

Arterial wall sulfated glycosaminoglycans (GAG) of matrix proteoglycans have been implicated in the retention of plasma low density lipoproteins in the early stages of atherosclerosis. We have studied modifications in porcine aortic GAG composition after 4 and 11 weeks of diet-induced hypercholesterolemia. After these time intervals no grossly visible atherosclerotic lesions were discerned. GAG changes were correlated with tissue LDL accumulation estimated by quantification of immunochemically-identifiable apolipoprotein B (apoB). Values of apoB ranged from less than 10 to 250 ng/mg wet weight of aorta, and correlated significantly with tissue total cholesterol contents. Although total GAG concentrations did not differ between a normolipemic control and the two diet groups, apoB showed a significantly positive correlation with the percent of total GAG that was chondroitin sulfate and a significantly negative correlation with the percent of total GAG that was dermatan sulfate. Total tissue cholesterol likewise demonstrated similar correlations with GAG. Since areas of the aorta were chosen that were devoid of intimal thickening, these metabolic changes may occur in the inner part of the arterial tunica media. The results suggest that the accumulation of plasma LDL in the arterial wall following hypercholesterolemia may induce alterations in arterial GAG composition, presumably by affecting GAG synthesis by medial smooth muscle cells.
Atherosclerosis 1986 Sep
PMID:Plasma low density lipoprotein accumulation in aortas of hypercholesterolemic swine correlates with modifications in aortic glycosaminoglycan composition. 309 51

Artery proteoglycan-lipoprotein binding characteristics were determined using intact, high molecular weight chondroitin sulfate proteoglycans (CS-PG) isolated from grossly appearing normal aortas of atherosclerosis susceptible WC-2 pigeons and plasma lipoproteins from normolipemic, randomly bred White Carneau pigeons. Optimum formation of particulate proteoglycan-lipoprotein complexes occurred in 5 mM Tris, 6 mM KCl, 4 mM CaCl2, 1 mM MgSO4, pH 7.2. The binding of CS-PG was specific for low density lipoprotein (LDL) and not high density lipoprotein (HDL). The relative importance of the intact monomeric structure of the PG was suggested in studies where glycosaminoglycan chains isolated from the PG monomer possessed less than 1% of the binding reactivity of the intact PG. The core protein prepared from the CS-PG monomer formed no measurable particulate complex.
Atherosclerosis 1987 May
PMID:Artery wall derived proteoglycan-plasma lipoprotein interaction: lipoprotein binding properties of extracted proteoglycans. 311 91

The binding of intact, high molecular weight, aortic proteoglycan (PG) isolated from grossly normal appearing aortas of atherosclerosis-susceptible White Carneau pigeons (WC-2) and -resistant Show Racer pigeons (SR) to homologous and heterologous serum lipoproteins from both normolipemic and hyperlipemic pigeons was examined. In vitro binding studies were done using a mixture of purified chondroitin sulfate PG and dermatan sulfate PG monomers to simulate an in situ composition. For each animal, a binding potential or reactivity number was calculated and corresponded to the shape and slope of the PG-LDL binding curve, where higher values indicated greater reactivity. For WC-2 normal sera, mean values were 0.97 and 0.95 using WC-2 and SR PG respectively, compared to SR normal sera (equivalent total plasma cholesterol) where values were 0.80 and 0.82. Corresponding mean reactivity values for hyperlipemic sera (diluted to a cholesterol concentration of 300 mg/dl) were 0.95, 1.00, 0.73, and 0.79. The results suggest that LDL from both normolipemic and hyperlipemic atherosclerosis-susceptible WC-2 pigeons is more reactive in complexing to artery wall derived PG than LDL from SR pigeons, regardless of PG source.
Atherosclerosis 1987 May
PMID:Lipoprotein interaction with artery wall derived proteoglycan: comparisons between atherosclerosis-susceptible WC-2 and resistant Show Racer pigeons. 311 92

We have experienced two autopsy cases of familial hypercholesterolemia of type IIa homozygote, one was a 21-year-old female with a defect in the internalization of low density lipoprotein which is thought to be the first autopsy report in the world, and the other was a 31-year-old male with a receptor negative for low density lipoprotein. Autopsy findings, in addition to marked skin xanthomatosis, disclosed reversed distribution of the aortic atherosclerosis, diffuse atherosclerotic narrowing of coronary arteries which led to myocardial necrosis, xanthomatous aortic and mitral valve, and much less severity of cerebral arteries rather than that of aorto-coronary atherosclerosis. We have examined the apolipoprotein B accumulation on these aortas, coronary arteries, and cardiac valves, which showed better correlation between apolipoprotein B deposit areas and preferential accumulation of Alcian blue positive areas suggested to contain sulfate glycosaminoglycan, and documented very rare localization of renal and osseous xanthomas in a patient with internalization defect of low density lipoprotein.
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PMID:Autopsy findings in two patients with homozygous familial hypercholesterolemia. Special references to apolipoprotein B localization and internalization defect of low density lipoprotein. 312 Apr 90

In the present study the biosynthesis of glycosaminoglycans (GAGs) by neonatal rat aortic smooth muscle cells in culture was studied. Heparan sulfate (HS) was the predominant GAG of the cell layer accounting for 32-49% of the total GAGs depending on the time in culture. The presence of low sulfated chondroitin sulfate (LSC) in aortic smooth muscle cell cultures is reported here for the first time. The effect of ascorbate on the synthesis and accumulation of these macromolecules resulted in a relative increase of C4S and DS in the cell layer. In contrast, the distribution of the GAGs which were secreted into the medium was not significantly effected by the addition of ascorbate. While HS was always found to be a minor component, the other GAGs were present in about equal concentrations. The total GAG accumulation in the medium was much greater (91-97%) than that of the cell layer (3-9%) indicating that the cells are synthesizing relatively large amounts of GAGs, although incorporation of these macromolecules into the extracellular matrix was consistently low.
Atherosclerosis 1988 Jan
PMID:Glycosaminoglycan content in neonatal rat aortic smooth muscle cell cultures. 312 1

Proteoglycan (PG) metabolism by aortic smooth muscle cell cultures derived from atherosclerosis-susceptible White Carneau (WC) and -resistant Show Racer (SR) pigeons was compared using [35S]sodium sulfate and [3H]serine or [3H]glucosamine as labeling precursors. Chondroitin sulfate (CS) PG and dermatan sulfate (DS) PG were the major PG secreted into the medium by both cell types. Total PG production, whether measured by incorporation of radiolabel into either core protein or glycosaminoglycan chains, was consistently lower in WC compared to SR cultures at several time points. This difference was due in part to lower (30-37%) PG synthesis in WC cells, but degradation of newly synthesized PG was an important contributor. A pulse-chase study indicated that of the total radiolabeled PG present at time O, only 47% was present at 24 h in WC cultures compared to 88% in SR cultures. The large CS-PG appeared to be the primary target for degradation in WC cells, and this selective processing resulted in a higher DS-PG:CS-PG ratio in these cultures. Structural studies indicated similar core protein and glycosaminoglycan chain sizes within a PG type for both cell types. PG monomer composition differed, however, by a higher sulfation of WC CS-PG compared to SR CS-PG and by a disaccharide sulfation position favoring 6-sulfation in WC PG and 4-sulfation in SR PG.
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PMID:Distinct synthetic and structural characteristics of proteoglycans produced by cultured artery smooth muscle cells of atherosclerosis-susceptible pigeons. 313 65


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