UMLS:C0004153 - FACTA Search

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Query: UMLS:C0004153 (atherosclerosis)
77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Carbohydrate composition of serum low and high density lipoproteins obtained from 5 nonhuman primate species (chimpanzee, patas, baboon, rhesus, and spider) and humans was studied. 2. Individual lipoproteins were isolated from pooled sera of each species by ultracentrifugal flotation between the densities 1.019-1.063 for LDL-2; 1.063-1.12 for HDL-2; and 1.12-1.21 for HDL-3. After delipidation, sialic acid, fucose, glucosamine, mannose, galactose, and glucose were determined on apo LDL-2, apo HDL-2, and apo HDL-3. 3. Glucosamine, galactose, and mannose constituted a major component of the sugars in apo LDL-2, with similar relative proportions in all species. Sialic acid, fucose, and glucose formed a minor component, the proportions of which varied greatly among the species. 4. Unlike apo LDL-2, sialic acid, fucose, and glucosamine constituted the bulk of the sugars in apo HDL-2 and apo HDL-3. Mannose, galactose, and glucose were minor components, with galactose predominating. 5. Qualitative differences were observed in electrophoretic mobilities of apo HDL-2 and apo HDL-3 on polyacrylamide gel. One faster moving band was unique to chimpanzee. 6. Intraspecies differences in the content of sialic acid and fucose of apolipoproteins may be related to lipoprotein metabolism and species susceptibility (or resistance) to either spontaneous or diet-induced atherosclerosis.
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PMID:Carbohydrate composition of serum low and high density lipoproteins of nonhuman primate species. 23 83

The properties of sialylated (sialic acid rich) and desialylated (sialic acid poor) fractions of low-density lipoproteins (LDL) isolated from blood plasma of healthy subjects and coronary atherosclerosis patients have been investigated. Sialylated (60-90% of total LDL) and desialylated (10-40%) LDL were separated by affinity chromatography on Ricinus communis agglutinin-agarose. Sialic acid contents in sialylated LDL fractions of healthy subjects and patients were found to be the same, and 1.5 to 3-fold higher than in desialylated LDL. Desialylated LDL had smaller sizes and greater electrophoretic mobility than sialylated, ones. Desialylated, but not sialylated, LDL induced 1.5 to 4-fold accumulation of neutral lipids in human aortic smooth-muscle cells. Desialylated LDL contained lower amounts of cholesteryl esters, free cholesterol and triglycerides as compared to sialylated LDL. On the other hand, the concentrations of di-, monoglycerides and free fatty acids in desialylated LDL were 2 to 3-fold higher than in sialylated lipoproteins. The desialylated LDL fraction was characterized by lower levels of phosphatidylcholine, sphingomyelin and phosphatidylethanolamine, but a higher content of lysophosphatidylcholine. Levels of thiobarbituric acid-reactive substances in freshly isolated desialylated and sialylated LDL were the same. Desialylated LDL had a higher level of oxysterols and lower amounts of vitamins A and E. The content of free amino groups of lysine in desialylated LDL of patients was 2-fold lower than in sialylated LDL. The results of this study demonstrate that multiple physico-chemical parameters of desialylated LDL differ from those of sialylated LDL.
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PMID:Characterization of desialylated low-density lipoproteins which cause intracellular lipid accumulation. 147 92

We have recently established that low density lipoprotein (LDL) of most patients with coronary atherosclerosis differs from the LDL of most healthy subjects by its ability to cause primary atherosclerotic changes, i.e. the accumulation of intracellular cholesterol in the cells of smooth muscle origin cultured from unaffected intima of human aorta. Patients' LDL has a 2.5-5-fold lower content of sialic acid as compared with the LDL of healthy subjects. On the other hand, desialylation of native LDL with neuraminidase makes it capable of causing accumulation of intracellular cholesterol similar to patients' LDL. In the present study we showed that LDL of patients and healthy donors did not differ in the content and composition of protein and lipids. Thus, the difference in the content of sialic acid is the only difference observed between atherogenic LDL of patients and nonatherogenic LDL of healthy donors. A low content of sialic acid is characteristic of both protein and lipid moiety of LDL particle. Sialic acid content was determined in individual LDL preparations obtained from patients and healthy donors. The sialic acid of LDL preparations of 25 out of 27 patients was below 18 micrograms/mg protein. LDL from 2 patients with higher sialic acid content proved to be normal. The ability of patients' LDL and LDL desialylated with neuraminidase in vitro to cause the accumulation of intracellular lipids correlated with the degree of lipoprotein desialylation. Apparently, the ability of patients' LDL to stimulate the cellular lipid accumulation may be explained by a deficiency of sialic acid in the lipoprotein particle.
Atherosclerosis 1991 Feb
PMID:Desialylated low density lipoprotein--naturally occurring modified lipoprotein with atherogenic potency. 187 10

The interaction of low density lipoproteins (LDL) with chondroitin sulfate-rich arterial proteoglycans appears to be initiated by coulombic interactions that lead to insoluble complexes. Once formed, large LDL aggregates are held together by non-polar associations. The irreversible formation of LDL proteoglycans aggregates was evaluated for different LDL preparations by definition of an avidity coefficient (Ar) using a Langmuir isotherm. LDL from different subjects, when tested against the same lipoprotein-complexing proteoglycan (LCP), gave Ar values ranging from 1-9 X 10(6) L/M. High avidity values were associated to lipoproteins with apparent isoelectric points above 6.5. These lipoproteins show low sialic acids content. The content of N-acetyl and N-acetyl,O-acetyl sialic acid was found inversely correlated with the avidity coefficient for the arterial LCP. Reductions of 42% on the LDL sialic acid content, by neuraminidase treatment, induced a 10-fold increment in their avidity for the lipoprotein complexing proteoglycan. The results indicate that at low ionic strength and physiological Ca2+-concentration and pH, the surface charge of LDL is an important modulator of the interaction with the arterial proteoglycan. Sialic acid, perhaps because of its exposure at the LDL surface, plays a determinant role in the in vitro association of LDL with the polyanionic proteoglycans. It is possible that in the intima-media the sialic residues of LDL and its balance of surface charges will control part of the interactions with the proteoglycans of the extracellular matrix.
Atherosclerosis 1985 Apr
PMID:Interaction of low density lipoproteins with arterial proteoglycans. The role of charge and sialic acid content. 400 85

In rabbits fed with hypercholesterolemic diet the normal coronary vasodilator response to serotonin is replaced by vasoconstriction sensitive to 5HT2 receptor blockade. These experiments were designed to determine the receptor subtype involved in the contractile response of large isolated coronary arteries (without endothelium) taken from control and atherosclerotic rabbits. In both tissues the agonists' rank potency was 5-carboxamidotryptamine > serotonin (5HT) > sumatriptan > 8-OHDPAT: (+/-)-8-Hydroxydipropylaminotetralin HBr > 2-methylserotonin. In arteries from young rabbits, 5HT and sumatriptan induced contractions which were not influenced by ketanserin up to 3 x 10(-8) M. However, the 5HT2 antagonist at the concentration of 10(-6) M induced a significant rightward shift of the concentration-response curves. The contractions to the two serotoninergic agonists were competitively inhibited by methiothepin. NAN 190, a 5HT1A antagonist, LY 53857, a 5HT1C and 5HT2 antagonist, cyanopindolol, a 5HT1A and 5HT1B antagonist and ICS 205-930, a 5HT3 and 5HT4 antagonist (up to 10(-6) M) did not inhibit the contractile response to 5HT. Rauwolscine (10(-6) M) significantly shifted the concentration-response curves to the two agonists. Very similar results were obtained in coronary arteries from atherosclerotic rabbits. These data demonstrate that in rabbit epicardial coronary artery smooth muscle, the receptor involved in the serotoninergic response is a 5HT1-like subtype, possibly a 5HT1D. In this preparation, under our experimental conditions, there was no evidence for the presence of 5HT2 receptors. The induction of atherosclerosis did not induce significant changes in the serotoninergic response in these large coronary arteries, illustrating the marked heterogeneity between microvasculature and large arteries in the rabbit heart.
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PMID:Serotoninergic receptor subtype in coronary artery smooth muscle from young and atherosclerotic rabbit. 830 47

Sialic acid-poor low density lipoprotein (LDL) is suggested to be atherogenic because it causes in vitro accumulation of cholesterol into epithelial cells and macrophages. We studied whether the whole-body catabolism of LDL varies according to its sialic acid content by analyzing the sialic acids in total (d 1.019-1.063 g/ml), light (d 1.019-1.036 g/ml), dense (d 1.037-1.055 g/ml), and very dense (d 1.056-1.063 g/ml) LDL, and the kinetics of total and dense LDL apolipoprotein (apo) B in 20 non-insulin-dependent diabetic and 10 non-diabetic men of similar age, both groups without and with coronary artery disease (CAD). The sialic acid/apoB ratio was significantly higher in the diabetics compared to the controls in every LDL fraction. Fractional catabolic rate (FCR) for LDL apoB was significantly faster in the diabetics than in the non-diabetics, and was positively associated with the sialic acid ratio in the total and dense LDL. In multiple linear regression analyses with FCR for total and dense LDL apoB as the dependent variable and the presence of diabetes, body mass index, LDL cholesterol, triglycerides, and sialic acid/apoB ratio as the independent variables, LDL cholesterol and serum triglycerides were the only variables entering significantly to these models. The sialic acid/apoB ratio of total and dense LDL was similar in subjects without and with CAD. These results suggest that in this population the sialic acid content of LDL was not associated with clinical signs of atherosclerosis, but the catabolic rate of dense LDL apoB was positively related to the sialic acid content of the respective lipoproteins.
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PMID:Sialic acids and the metabolism of low density lipoprotein. 886 46

The sialic acid content of electronegative low density lipoprotein (LDL) and LDL isolated from human aortic intima was measured. Sialic acid level in electronegative LDL of healthy subjects was 1.7-fold lower than in native LDL. Sialic acid content in electronegative LDL of coronary atherosclerosis patients was 3-fold lower than in native LDL. Lipoproteins isolated from grossly normal human aortic intima and from fatty streaks contained 20-56% less sialic acid as compared to blood plasma LDL. A negative correlation was established between the ability of electronegative and aortic LDL to stimulate lipid accumulation in cells cultured from uninvolved human aortic intima and lipoprotein sialic acid content. The results obtained indicate that electronegative and aortic LDLs have a low sialic acid content, i.e., are desialylated lipoproteins. Considered together with the fact that all known atherogenic LDLs have similar characteristics, our findings suggest that modified LDLs are the same lipoprotein particles subjected to multiple modification.
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PMID:Similarity between naturally occurring modified desialylated, electronegative and aortic low density lipoprotein. 888 95

The specific interaction of lipoproteins with arterial wall constituents, particularly proteoglycans (APG), is believed to play an important role in the development of atherosclerosis. The objective of this study was to examine the interaction of apolipoprotein B (apoB) containing lipoprotein subfractions (VLDL1, Sf 60 to 400; VLDL2, Sf 20 to 60; IDL1, Sf 16 to 20; IDL2, Sf 12 to 16; LDLA, Sf 8 to 12; and LDLB, Sf 0 to 8) prepared by cumulative density gradient centrifugation with chondroitin sulfate-rich APG. Eighteen subjects were studied, and a similar pattern of interaction between the lipoprotein species and APG was found in all. The order of reactivity (as measured by increased turbidity due to insoluble complex formation) was IDL Sf 12 to 16 > or = LDL Sf 8 to 12 > LDL Sf 0 to 8 > IDL Sf 16 to 20 >> VLDL Sf 20 to 60 > VLDL Sf 60 to 400. When the subjects were divided on the basis of their LDL subfraction profile, the extent of insoluble complex formation was highest in the group in which small, dense LDLIII was predominant; intermediate in the group whose LDL was mainly LDLII; and lowest in the group with a high proportion of LDLI (the mean reactivity, AU at 600 nm. of APG with IDL Sf 12 to 16 and LDL Sf 8 to 12 was 0.66; 0.62 and 0.46, 0.43 and 0.20, and 0.21 for the three groups, respectively). Fibrate lipid-lowering treatment decreased the percentage of LDLIII and increased the percentage of LDLI within total LDL and reduced the reactivity of all apoB-containing lipoprotein fractions toward APG. Sialic acid content varied in different lipoprotein subfractions, being the highest in VLDL and lowest in LDL. However, across lipoprotein species, it did not significantly correlate with APG-binding reactivity, suggesting that other factors are important in determining the interaction of lipoproteins with APG. Modification of LDL arginine and lysine residues abolished the ability of the lipoprotein to interact with APG, a finding that supports the hypothesis that the interaction is dependent on key positively charged amino acids on apoB. These findings demonstrate that (1) the overall reactivity of apoB-containing lipoproteins is greatest in individuals with small, dense LDL and (2) within an individual, IDL of Sf 12 to 16 is the most reactive species, and this may in part explain the positive correlation between IDL and risk of coronary heart disease.
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PMID:Interaction of very-low-density, intermediate-density, and low-density lipoproteins with human arterial wall proteoglycans. 940 21

Sialic acid level in blood plasma and circulating glycoproteins is considered to be a marker for a number of pathologic conditions, including atherosclerosis, cancer, etc. The precise measurement of sialic acid level is an important laboratory procedure to allow correct interpretation of results. Colorimetric methods commonly used for the measurement of sialic acid are not highly specific, as interfering substances may alter the results. Among these, malondialdehyde and other aldehydes play the decisive role. In the circulation, aldehydes are commonly produced during lipid peroxidation in the lipid core of lipoprotein particles, especially low density lipoprotein (LDL). To establish the impairment to the sialic acid determination in LDL introduced by interfering substances, the optimized assay based on Warren's traditional method was developed and tested in 606 LDL samples. The optimization implies the comparison of color developed using the standard Warren procedure with that due to contaminating agents, mainly thiobarbituric acid-reactive substances (TBARS). In LDL stored at 4 degreesC, the estimates obtained by the modified procedure were 41.5% or 30.1 nmol/mg lower, on average, compared to the standard procedure (n = 45, P < 0.0001). Even in LDL stored at -70 degreesC, sialic acid estimates obtained by the modified procedure were 6.6% or 3.6 nmol/mg lower, on average, compared to the standard measurement (n = 561, P < 0.005). Thus, the modified procedure avoids significant distortion of the measurement induced by the presence of interfering agents.
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PMID:Optimization of the assay for sialic acid determination in low density lipoprotein. 979 16

Sialic acid is a negatively charged sugar associated with the protein and lipid portions of lipoproteins. Sialic acid has been hypothesised to play an anti-atherogenic role in lipoprotein metabolism through the electrostatic inhibition of lipoprotein interactions with chondroitin-6-sulphate-rich arterial proteoglycans (APG). We conducted a series of studies using native and modified lipoproteins (VLDL1 Sf 60-400, VLDL2 Sf 20-60, IDL1 Sf 16-20, IDL2 Sf 12-16, LDL(A) Sf 8-12, and LDL(B) Sf0-8) that vary in their sialic acid content to examine the relationship between lipoprotein sialic acid content and its interaction with APG. Lipoprotein sialic acid was greatest in VLDL1 and decreased progressively with particle density until the IDL2 fraction (VLDL1 > VLDL2 > IDL1 > IDL2 = LDL(A) = LDL(B)). The pattern of reactivity of each fraction with APG was different from the pattern observed for lipoprotein sialic acid content (IDL2 > LDL(A) > LDL(B) > IDL1 > VLDL2 > VLDL1). Levels of sialic acid were lower in subjects with CHD as compared to control subjects but the presence of CHD had no effect on lipoprotein-APG complex formation when sex and plasma triglyceride levels were taken into account. There was also no significant relationship between the lipoprotein sialic acid content and the reactivity with APG within each lipoprotein fraction. Treatment of hypertriglyceridaemic subjects with ciprofibrate decreased lipoprotein-APG complex formation in all lipoprotein fractions. This was associated with a decrease in the total sialic acid content of apo B100-containing lipoproteins suggesting that the total sialic acid content of apo B100-containing lipoproteins has no influence on lipoprotein-APG complex formation. We next conducted in vitro experiments to manipulate LDL sialic acid content. Enzymatic removal of sialic acid from LDL with neuraminidase resulted in an increase in LDL-APG complex formation. This was accompanied by an increase in the exposure of free amino groups on LDL possibly due to disruption of interactions between free amino groups and sialic acid-containing components on LDL. Increasing LDL sialic acid content through incubation with ganglioside resulted in a decrease in lipoprotein-APG complex formation without any changes in the exposure of free amino groups on LDL. We conclude that total sialic acid content of lipoproteins is not a major determinant of their binding to APG. However, specific sialic acid-containing components on lipoproteins can affect their interaction with APG.
Atherosclerosis 1999 Aug
PMID:Sialic acid-containing components of lipoproteins influence lipoprotein-proteoglycan interactions. 1048 50

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