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)

The concentration and composition of proteoglycans (PG) of the neointima developed following balloon catheter removal of aortic endothelium in rabbits, were assessed. PG were extracted from the aortic intimal-medial tissues with 4 M guanidinium chloride in the presence of protease inhibitors and purified subsequently by cesium chloride gradient ultracentrifugation and fractionation by high-performance liquid chromatography (HPLC). PG so obtained was analysed for its protein, cholesterol and glycosaminoglycan (GAG) content. For the characterization of the GAG moiety, an exhaustive proteolytic digestion was done. The GAG were then recovered by ethanolic precipitation and their relative distribution was determined after a selective enzymatic digestion using specific enzymes. Results show a significant increase in the amount of PG in the areas of the injured arterial wall covered by regenerated endothelium. In addition, changes in the composition of GAG were also found in the PG isolated from experimental animals when compared to PG isolated from normal aorta. A marked increase in the content of chondroitin sulfates and dermatan sulfate of injured tissue was seen. Hyaluronic acid content also changed in response to de-endothelialization and cholesterol feeding, but only moderately. The content of heparan sulfate remained unaffected in experimental tissues. Furthermore, cholesterol feeding aggravated the injury-induced increment of GAG. These findings are consistent with previously reported morphological observations, and correlate well with reports that arterial injury and cholesterol feeding act synergistically in the evolution of the atherosclerotic lesion and provide further evidence that the interaction of lipid and PG of the arterial wall may be of particular importance to our comprehension of the pathogenesis of atherosclerosis.
Atherosclerosis 1987 Jan
PMID:Proteoglycan composition of rabbit arterial wall under conditions of experimentally induced atherosclerosis. 382 71

The low-density lipoproteins (LDL)-glycosaminoglycans (GAG) complexes were isolated from fibrous plaques, fatty streaks and normal of human aortic intima and analysed for lipids and GAGs. The LDL-GAG complexes formed a precipitation line against antihuman apoprotein B, which is a major component of plasma LDL, and the lipids constituents of LDL-GAG complexes resembled those of plasma LDL. It might be suggested from these findings that the lipoproteins (LP) bound to GAG in arterial tissue was originated from plasma LDL penetrated into arterial tissue from circulating system. From the analysis of GAGs in LDL-GAG complexes by two-dimensional electrophoresis, the % composition of GAG in fibrous plaques showed higher in chondroitin-4-sulfate (CS-4-S) plus chondroitin-6-sulfate (CS-6-S) and marked lower in dermatan sulfate (DS) when compared with those of fatty streaks. There are no differences in the % composition of hyaluronic acid (HA) in normal and atherosclerotic lesions. It would be suggested from these observations that the formation of saline extractable LDL-GAG complexes would be the early events in aortic intima when plasma LDL penetrated from circulation system and that not only DS and/or heparan sulfate (HS) but also CS-4-S and/or CS-6-S have an important role on the progression of atherosclerosis.
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PMID:The analysis of lipids and glycosaminoglycans of low-density lipoprotein-glycosaminoglycans complexes isolated from normal, fatty streaks and fibrous plaques of human aortic intima. 383 14

Proteoglycans accumulate within the innermost layer (intima) of blood vessels during atherosclerosis. This accumulation is marked in some forms of human atherosclerosis and is particularly prominent in vessels that have been experimentally injured and have healed by the process of reendothelialization. The two major cell types of the arterial wall, endothelium and smooth muscle, are the major sources of arterial proteoglycans, and cell cultures have demonstrated that these cells synthesize at least three families of proteoglycans similar to those present in human aorta. Each family differs with regard to molecular size, glycosaminoglycan and oligosaccharide content, and ability to aggregate in the presence of hyaluronic acid. Furthermore, each cell type possesses a distinct pattern of proteoglycan synthesis. Smooth muscle cells synthesize and secrete primarily chondroitin sulfate and dermatan sulfate-containing proteoglycans, whereas endothelial cells synthesize and secrete large amounts of heparan sulfate proteoglycan. Evidence is presented to indicate that the synthesis of proteoglycans is modulated as a function of growth and migratory state of the vascular cells.
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PMID:Proteoglycans in pathological conditions: atherosclerosis. 388 Dec 92

To elucidate whether or not a vitamin E-deficient diet affects the rat aorta extracellular matrix, we examined the alterations in glycosaminoglycans (GAGs), as one of the components of the extracellular matrix of the aorta. The total amount of uronic acid, as an index of GAG, decreased significantly in the aorta of vitamin E-deficient rats. The components of GAG were identified as hyaluronic acid (HA), heparan sulfate (HS), dermatan sulfate (DS) and chondroitin sulfate (CS) by electrophoresis together with enzymic digestion. The amount of sulfated GAGs, especially the amount of DS and CS, decreased in the aorta of vitamin E-deficient rats. The biosynthetic activity of GAG was determined by using [3H]glucosamine and [35S]sulfate. The total biosynthetic activity of GAG and the incorporation of [3H]glucosamine into HA, HS, DS and CS decreased markedly in the aorta of vitamin E-deficient rats. The decrease in the production of sulfated GAGs, especially DS, which is involved in the potent antithrombogenic activity, could be related to the lower anticoagulant activity in the aorta of vitamin E-deficient rats.
Atherosclerosis 1985 Apr
PMID:Alterations in glycosaminoglycans of the aorta of vitamin E-deficient rats. 392 63

Arterial dermatan sulfate proteoglycans (DS-PG) were isolated from randomly bred White Carneau (RBWC) pigeons and a line of White Carneau pigeons (WC-2) genetically selected for increased atherosclerosis susceptibility. To characterize the basic proteoglycan (PG) structure and to identify structural differences that may relate to a specific arterial phenotype, embryos were labeled with radioactive sulfate in ovo and PG were isolated from aortas with 4.0 M GdnHCl. DS-PG were separated from chondroitin sulfate PG by gel chromatography and further purified by CsCl buoyant density ultracentrifugation and ion-exchange of chromatography. The DS-PG monomers from the two genetic lines of pigeons eluted at different positions on two high pressure liquid chromatography (HPLC) gel permeation systems, which suggested a structural difference between the two monomers. Analysis of the monomer components showed a similar protein core molecular weight of 50,000 for each and a similar amino acid composition. Glycosaminoglycans (GAG) molecular weights were estimated to be 15,000 for WC-2 and 18,000 for RBWC. The findings suggest a basic difference in post-translational processing of PG in the two pigeon types which may reflect distinct functional properties associated with resistance or susceptibility to atherosclerosis.
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PMID:Arterial dermatan sulfate proteoglycan structure in pigeons susceptible to atherosclerosis. 396 3

Glycosaminoglycans (GAG) are believed to be important in the pathogenesis of atherosclerosis. We have previously demonstrated that areas of injured aorta that have been re-endothelialized accumulate increased amounts of lipid and GAG when compared to areas remaining de-endothelialized. We have now examined the net incorporation of labeled precursors into the individual GAG present in both re-endothelialized and de-endothelialized areas of rabbit aorta. Aortic tissue was examined at 2-3 and 10-14 weeks after a denuding injury by incubating tissue minces with [3H]glucosamine and sodium [35S]sulfate for 24 hr. Following incubation, the aortic GAG were isolated and assayed for uronic acid concentration and radioactivity. Results indicate that the total GAG concentration was significantly greater (P less than 0.001) in the re-endothelialized (9.46 +/- 0.29 micrograms/mg lipid-free dry residues (LFDR), mean +/- SE) as compared to de-endothelialized (7.89 +/- 0.43 micrograms/mg LFDR) areas. The concentration in uninjured aorta was 9.01 +/- 0.69. The difference between the injured tissues was attributable to increased concentrations of sulfated GAG. Hyaluronic acid and chondroitin sulfate were the most metabolically active of the GAG in either uninjured or injured aorta, together accounting for over 75% of the 3H label. The 3H specific radioactivities of the four GAG in the short-term, re-endothelialized subgroup were all increased nearly twice that found in uninjured and de-endothelialized tissues. With the exception of heparan sulfate, no significant differences were noted in the 3H specific radioactivities between the re-endothelialized and de-endothelialized areas in the long-term subgroup. These results indicate that, relative to adjacent areas of de-endothelialization, GAG preferentially accumulate in re-endothelialized areas even as early as 2-3 weeks following a denuding injury. Overall, metabolic data suggest that increased synthesis is responsible for this effect, although the net contribution of degradative processes cannot be overlooked since GAG turnover was not specifically examined. Thus, it is possible that regenerated endothelium may modify the GAG metabolism of the arterial wall following arterial injury.
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PMID:Altered glycosaminoglycan metabolism in injured arterial wall. 399 53

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

The [35S]glycosaminoglycans ([35S]GAG) synthesized by capillary endothelial cells were analyzed and compared to GAG synthesized by endothelial cells cultured from 4 larger vessels. Two separate cultures of endothelial cells were established from bovine fat capillaries and from 4 larger vessels of human origin (umbilical vein) and bovine origin (pulmonary artery, pulmonary vein and aorta). After incubation with 35SO4 for 72 h, the [35S]glycosaminoglycans (GAG) composition of the media, pericellular and cellular fractions of each culture were determined by selective degradation with nitrous acid, chondroitinase ABC and chondroitinase AC. All endothelial cells produced large amounts of [35S]GAG with increased proportions of heparinoids (heparan sulfate and heparin) in the cellular and pericellular fractions. Each culture showed a distinct distribution of [35S]GAG in the media, pericellular and cellular fractions with several specific differences found among the 5 cultures. The differences in GAG content were confirmed in a second group of separate cultures from each of the 5 vessels indicating that, although having several features of GAG metabolism in common, each endothelial cell culture demonstrated a characteristic complement of synthesized, secreted and cell surface-sulfated glycosaminoglycans.
Atherosclerosis 1985 Jul
PMID:Sulfated glycosaminoglycans in cultured endothelial cells from capillaries and large vessels of human and bovine origin. 402 33

We have described methodology for the isolation and quantitation of glycosaminoglycans present in human plasma. Plasma glycosaminoglycans can be quantitatively adsorbed on a DEAE-Sephacel ion exchanger and eluted with a salt gradient as two groups: a low-charge fraction and a high-charge fraction. The low-charge fraction consists of chondroitin sulfate with a low sulfate content and the high-charge fraction consists of heparan sulfate, chondroitin sulfate, and keratan sulfate (type I). We have determined the plasma concentration of each of these glycosaminoglycans in six normal human subjects. We have established that none of the glycosaminoglycans in plasma are covalently linked to plasma proteins. All are isolated as complexes with plasma proteins in noncovalent linkages. The glycosaminoglycans in the low-charge fraction are bound with high affinity to a single plasma glycoprotein by a lectin-type bond that can be disrupted by a simple glycoside. The high-charge fraction contains three major proteins and several minor proteins associated with the glycosaminoglycans by both lectin-type and ionic bonding. The plasma proteins associated with glycosaminoglycans represent less than 0.5% of the total plasma proteins. Little is known about the physiologic role of the plasma glycosaminoglycans as components of metabolic processes. Because glycosaminoglycans have been implicated in lipid metabolism and atherosclerosis, we tested all of these compounds, isolated in free form, on the in vitro hydrolysis of triglycerides by lipoprotein lipase. Plasma heparan sulfate stimulated the rate of this reaction severalfold. All other plasma glycosaminoglycans were inactive. Thus, plasma heparan sulfate may play an important role in plasma lipoprotein metabolism.
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PMID:Isolation and characterization of glycosaminoglycans in human plasma. 405 61

The mechanisms of atherogenesis are under intensive clinical and experimental investigation. It is commonly accepted that lipoproteins play a major role in atherogenesis. The results of several clinical studies suggest that lipoprotein (a) [Lp(a)] represents an independent risk factor for atherosclerosis. In order to obtain information on the physiological and pathological role of Lp(a), studies were undertaken to investigate the metabolism, removal sites, and possible atherogenic mechanisms of Lp(a). It was found that Lp(a) is not a metabolic product of other apoprotein B containing lipoproteins, but appears to be synthesized as a separate lipoprotein. The turnover parameters of Lp(a) resemble those of LDL. Binding studies of Lp(a) with cultured human fibroblasts demonstrated that Lp(a) is bound by the B-E receptor. After binding, Lp(a) is internalized and inhibits cellular cholesterol synthesis. In the presence of dextran sulfate or antibodies to the specific Lp(a) apoprotein or apoprotein B, Lp(a) is avidly taken up by macrophages. A similar mechanism might be responsible for the atherogenic effect of Lp(a).
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PMID:[Metabolism and possible mechanisms of atherogenesis induced by lipoprotein (a)]. 609 45


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