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

Water and glycosaminoglycan contents were measured in upper and lower thoracic aortas of claves and steers. The ability of various molarities of guanidine hydrochloride to extract glycosaminoglycans from these tissues was assessed. Some glycosaminoglycans seem to be more resistant to extraction than others. A procedure is described for the isolation of a proteoglycan. The molecule appears to contain both dermatan sulfate and chondroitin sulfate. It also seems to be less dense than cartilage proteoglycans extracted by similar methods as assessed by its behavior in centrifugal fields. The properties, locus and biological activities of this molecule are currently being studied.
Atherosclerosis
PMID:The ground substance of the arterial wall. Part 1. Extractability of glycosaminoglycans and the isolation of a proteoglycan from bovine aorta. 12 95

Electron microscopy of ruthenium red stained bovine aorta before and after chondroitinase digestion demonstrates proteoglycans on and between collagen fibrils. The collagen-associated proteoglycans include a proteoglycan previously purified from this tissue as demonstrated by immunocytochemistry and are extractable with high molar guanidine HC1. In loci rich in proteoglycans such as areas of turbulent flow in calves, more proteoglycan can be demonstrated morphologically, and these molecules also coat elastin.
Atherosclerosis
PMID:The ground substance of the arterial wall. Part 2. Electron-microscopic studies. 13 92

We studied the effect of heparin on proteoglycan synthesis by bovine aortic smooth muscle cells in culture. Confluent, growth-arrested cells were incubated with [35S]sulfate, [3H]glucosamine or [3]serine in the presence of 0-600 micrograms/ml heparin. Metabolically labeled proteoglycans secreted into the culture medium and associated with the cell layer were analyzed. In cultures treated with heparin there was a dose-dependent increase in [35S]sulfate incorporation into secreted proteoglycans which reached a maximum (35% above controls) at 100 micrograms/ml heparin. At higher concentrations of heparin, the stimulatory activity declined and finally disappeared. Radioactivity in cell-associated proteoglycans increased significantly (16% above controls) only in cultures treated with 100 micrograms/ml heparin. Heparin also produced similar increases in the incorporation of [3H]glucosamine and [3H]serine into secreted and cell-associated proteoglycans. While chondroitin sulfate, dermatan sulfate and heparan sulfate were elevated in the media, only chondroitin sulfate and heparan sulfate were increased in the cell layer. Heparin did not alter the degradation of proteoglycans. Heparin, while inhibiting the proliferation of subconfluent smooth muscle cells, also stimulated to a greater extent the incorporation of [35S]sulfate into proteoglycans. Other glycosaminoglycans, such as heparan sulfate, dermatan sulfate, heparin hexasaccharide and Sulodexide caused a significant but lesser stimulation of proteoglycan synthesis, while chondroitin sulfates and hyaluronic acid had no effect. Gel filtration chromatography of proteoglycans and their constituent glycosaminoglycans from heparin-treated and untreated cultures showed no differences in their molecular size. The results indicate that heparin can stimulate proteoglycan synthesis by vascular smooth muscle cells irrespective of their state of proliferation. This might have implications in vessel wall repair and arterial wall lipid deposition.
Atherosclerosis 1992 Jun
PMID:Heparin stimulates proteoglycan synthesis by vascular smooth muscle cells while suppressing cellular proliferation. 163 67

Cell surface proteoglycans of aortic smooth muscle cells of atherosclerosis-susceptible White Carneau (WC) and atherosclerosis-resistant Show Racer (SR) pigeons were compared to determine differences that may be involved in the greater proliferative properties of cultured WC cells. Using [35S]-sodium sulfate and [3H]-glucosamine as labeling precursors, chondroitin sulfate-proteoglycan (CS-PG) and heparin sulfate-proteoglycan (HS-PG) were identified as distinct molecules associated with the plasma membrane. Heparan sulfate-proteoglycan was reduced up to 50% in WC compared with SR cells, and, based on interaction with ion-exchange resin, had a lower charge density. These differences were not observed for the CS-PG from the two cell types. The mode of association of the cell surface PG with the plasma membrane was examined. Dissociation with 1 mol/l (molar) sodium chloride indicated that less than 10% of total cell surface PG were ironically associated with the cells. The remainder required detergent extraction, suggesting hydrophobic interactions with the plasma membrane. Both CS-PG and HS-PG displayed affinity for octyl sepharose and both were identified in isolated plasma membranes. These data present the first description of a hydrophobic CS-PG that is a significant and distinct cell-associated PG in arterial smooth muscle cells. The observation of decreased and structurally altered HS-PG in WC compared with SR cells is consistent with a potential growth regulatory function for this molecule.
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PMID:Cell surface heparan sulfate proteoglycan and chondroitin sulfate proteoglycan of arterial smooth muscle cells. 173 24

The interactions between serum lipoproteins isolated from rabbits fed a cholesterol-supplemented diet for six weeks, and soluble extracts of arterial neointima enriched in proteoglycans extracted from normocholesterolaemic rabbit aortas, were studied in an in vitro system. Neointimal tissues of rabbit aorta, which developed during three months following a selective endothelial injury, were excised and the areas covered or uncovered by regenerated endothelium were separated. To isolate the proteoglycan enriched fraction, both normal and injured tissue was homogenized in a sucrose solution containing protease inhibitors, centrifuged, and further fractionated by gel exclusion chromatography. The composition of the soluble extracts and each of their corresponding proteoglycan enriched fractions were analyzed in terms of protein and glycosaminoglycan content. Lipoproteins of donor animals fed an atherogenic diet were prepared by sequential ultracentrifugal flotation after density adjustment with KBr. Aliquots of electrophoretically pure lipoprotein fractions were incubated with proteoglycan enriched fraction from uninjured, denuded, or endothelium-covered neointima in the presence of Ca++ and Mg++ at 4 degrees C. The complexes formed during incubation were separated by centrifugation. The cholesterol content of the complexes was considered as an index of binding capacity. Results were expressed as micrograms of cholesterol bound per mg of glycosaminoglycan. The data reveal the higher affinity of hypercholesterolaemic lipoprotein fractions for aortic proteoglycans, as compared to normocholesterolaemic lipoproteins. In addition, when evaluating the relevance of the proteoglycan enriched fraction source, the affinity of fractions extracted from aortic neointima was found to be much higher for hypercholesterolaemic lipoproteins. These results suggest the role that proteoglycan-lipoprotein interactions could play in the event of the combined actions of endothelial injury and hypercholesterolaemia in the pathogenesis of atherosclerosis.
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PMID:Dietary alterations of plasma lipoproteins influence their interactions with proteoglycan enriched extracts from neointima of normal and injured aorta of rabbit. 174 20

The involvement of sulphated glycosaminoglycans in atherosclerotic changes have been studied in human and rat arteries, and biochemical experiments have revealed that a significant increase in the contents of chondroitin sulphate/dermatan sulphate and cholesterol, but loss of heparan sulphate, occurs in human atherosclerotic arterial tissues. Electron micrographs have revealed that extracellular deposits of lipid are predominantly present in areas rich in chondroitin sulphate proteoglycans but not in areas rich in collagen bundles and dermatan sulphate proteoglycans. The different types of proteoglycans have been distinguished in situ by the cuprolinic blue staining method and enzymatic degradation experiments, and their topohistochemical distribution patterns analysed by morphometry of proteoglycan/cuprolinic blue precipitates. The ultracytochemical investigations indicate changes in size and pattern of chondroitin sulphate-rich proteoglycan-cuprolinic blue precipitates in human atherosclerosis. In plaque tissue, these precipitates are significantly enlarged. In addition, they accumulate around smooth muscle cells in the medial tissue. An increase in the size of proteoglycan-cuprolinic blue precipitates has also been observed in balloon catheter-induced lesions in rat carotid arteries. The large chondroitin sulphate as well as the small dermatan sulphate proteoglycan-cuprolinic blue precipitates show this alteration 2 weeks after balloon injury. We suggest that quantitative and qualitative alterations in the arterial proteoglycans occur in the pathogenesis of atherosclerosis in addition to the cell proliferation and lipid accumulation.
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PMID:Mapping of proteoglycans in atherosclerotic lesions. 222 32

Arterial dermatan sulfate proteoglycan has been shown to increase with atherosclerosis progression, but factors responsible for this increase are unknown. To test the hypothesis that smooth muscle cell proteoglycan synthesis may be modified by macrophage products, pigeon arterial smooth muscle cells were exposed to the media of either cholesteryl ester-loaded pigeon peritoneal macrophages or a macrophage cell line P388D1. Proteoglycans radiolabeled with [35S]sulfate and [3H]serine were isolated from culture media and smooth muscle cells and purified following precipitation with 1-hexadecylpyridinium chloride and chromatography. Increasing concentrations of macrophage-conditioned media were associated with a dose-response increase in [35S]sulfate incorporation into secreted proteoglycans, but there was no change in cell-associated proteoglycans. Incorporation of [3H]serine into total proteoglycan core proteins was not significantly different (5.2 X 10(5) dpm and 5.5 X 10(5) disintegrations per minute (dpm) in control and conditioned media-treated cultures, respectively), but selective effects were observed on individual proteoglycan types. Twofold increases in dermatan sulfate proteoglycan and limited degradation of chondroitin sulfate proteoglycan were apparent based on core proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Immunoinhibition studies indicated that interleukin-1 was involved in the modulation of proteoglycan synthesis by macrophage-conditioned media. These data provide support for the role of macrophages in alteration of the matrix proteoglycans synthesized by smooth muscle cells and provide a mechanism to account for the reported increased dermatan sulfate/chondroitin sulfate ratios in the developing atherosclerotic lesion.
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PMID:Macrophage secretory products selectively stimulate dermatan sulfate proteoglycan production in cultured arterial smooth muscle cells. 231 26

The aortic lesions induced in normal-fed rabbits by an indwelling catheter were examined for changes in lipid content shown by oil red O-stained sections and associated proteoglycan distribution and ultrastructural changes by transmission electron microscopy of ruthenium red-stained sections, during an 8-week period of regression. Compared to normal aorta there was a highly significant increase in proteoglycan in lipid-containing lesions, which was also associated with the presence of regenerated endothelium. In the lesions which had regressed in terms of size and lipid content, the proteoglycan concentration, especially in superficial regions, was significantly reduced compared to early lesions and was similar to that seen in the normal vessel. Proteoglycan concentration decreased before lipid content of lesions was reduced. Proteoglycan was not associated with lipid-containing macrophages. These observations support the hypothesis that an increased glycosaminoglycan concentration is associated with lipid deposition in the vessel wall in response to injury in the absence of hyperlipaemia.
Atherosclerosis 1985 Jun
PMID:Proteoglycan distribution in catheter-induced aortic lesions in normolipaemic rabbits. An ultrastructural study. 240 88

Aortas from normal healthy rabbits, approx. 3 months old, were examined by light and transmission electron microscopy. The proteoglycan of the extracellular matrix, which was stained by ruthenium red and appeared as granules by transmission electron microscopy, was quantitated morphometrically in the intima and the superficial media. The intima included areas which were thickened and which contained connective tissue, including proteoglycan, and some smooth muscle cells. In the thickened intima there was a greater proportion of extracellular space which was occupied by proteoglycan, and the proteoglycan was present in higher concentration than in the media. In the aortas of rabbits, approx. 2 years old, the extent of intimal thickening and the concentration of proteoglycan increased in the thickened intima but there was no evidence of extracellular lipid deposition. The endothelial basement membrane contained small proteoglycan granules (heparan sulphate) which decreased in concentration in older animals. It is possible that the accumulation of proteoglycan in the thickened intima increases the susceptibility of the intima to accumulate lipid following an additional stimulus, such as hyperlipaemia, in the initial stages of atherosclerosis.
Atherosclerosis 1988 Jun
PMID:Proteoglycan distribution in the intima and media of the aortas of young and aging rabbits: an ultrastructural study. 245 67

The effect of mast cell stimulation on the uptake of low density lipoproteins (LDL) by macrophages was tested in vivo in the peritoneal cavity of the rat, a site known to contain both macrophages and mast cells. The concentration of LDL in the peritoneal cavity was raised by injecting [14C]sucrose-labeled LDL ([14C]sucrose-LDL). In the treated rats, in the absence of mast cell stimulation, the uptake of LDL by the peritoneal macrophages was low. But when the peritoneal mast cells were concomitantly stimulated by intraperitoneal administration of compound 48/80, an agent known to induce mast cell degranulation, the rate of uptake of labeled LDL by macrophages rose by 7-24-fold. The reason for this rise was that exocytosed mast cell granules bound LDL and carried it into macrophages when phagocytosed. Thus, cyclohexanedione treatment of LDL, or injection of avidin along with LDL, 2 measures known to inhibit binding of LDL to mast cell granules, totally prevented the mast cell-dependent uptake of LDL. Furthermore transmission electron microscopic studies with gold-labeled LDL disclosed phagocytosis of LDL-bearing granules by the peritoneal macrophages. This is the first demonstration of a natural proteoglycan being able to enhance the rate of LDL uptake by macrophages in vivo. These observations on the relation between stimulation of mast cells and uptake of LDL by macrophages in vivo may have relevance in other sites where mast cells and macrophages coexist, such as the arterial intima.
Atherosclerosis 1989 Oct
PMID:Stimulation of rat peritoneal mast cells enhances uptake of low density lipoproteins by rat peritoneal macrophages in vivo. 259 29


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