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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.02 seconds)

Although proteoglycans constitute a minor component of vascular tissue, these molecules have been shown to influence a number of arterial properties such as viscoelasticity, permeability, lipid metabolism, hemostasis, and thrombosis. A hallmark of early and late atherosclerosis is the accumulation of proteoglycans in the intimal lesions. Yet, it is not clear why this accumulation occurs. This article reviews the classes of proteoglycans synthesized by the two major cell types of the arterial wall--the endothelial and smooth muscle cell. Detailed consideration is then given to the modulation of proteoglycan metabolism and the role that proteoglycans play in a number of cellular events such as adhesion, migration, and proliferation--important processes in both the development and the pathogenesis of blood vessels. Last, the involvement of proteoglycans in two critical vascular wall processes--hemostasis and lipid metabolism--is reviewed, because these events pertain to atherogenesis. This review emphasizes the importance of proteoglycans in regulating several key events in normal and pathophysiological processes in the vascular tissue.
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PMID:Cell biology of arterial proteoglycans. 264 20

The complex formation of LDL with arterial proteoglycan or glycosaminoglycan was quantitated as precipitation of LDL-cholesterol after incubation in a low ionic strength buffer containing CaCl2 and MgCl2. It was found that human plasma or serum contains a factor which inhibits this complex formation. Upon density gradient centrifugation this factor was found at d greater than 1.24 g/ml. It could be further purified from the d greater than 1.24 g/ml fraction by affinity chromatography on heparin-Sepharose and hydrophobic interaction chromatography on phenyl-Sepharose. The content of inhibitory activity was found to vary over a 4-fold range in sera of apparently healthy persons.
Atherosclerosis 1989 Aug
PMID:Factor, present in plasma, inhibiting the interaction of low density lipoprotein with arterial proteoglycan. 278 98

An in vitro binding system was used to determine whether increases in LDL particle size and altered LDL chemical composition accompanying increased plasma cholesterol concentrations result in greater association of LDL with artery proteoglycan (PG) and whether the binding is related to atherosclerosis. LDL isolated from hypercholesterolemic atherosclerosis-susceptible White Carneau and resistant Show Racer pigeons was complexed to purified White Carneau pigeon aorta-derived high molecular weight PG under conditions whereby PG monomers were saturated. Using LDL of molecular weight greater than 5.0 x 10(6) daltons from both pigeon breeds, an inverse correlation between LDL size and the number of LDL particles bound per micrograms PG was demonstrated (r = 0.87, P less than 0.01). This relationship was attributed to the increased size of the LDL particle rather than any modification in chemical composition known to occur when LDL size increases, suggesting the major effect was attributed to steric hindrance. White Carneau pigeons with high molecular weight LDL had more severe atherosclerosis and the PG-LDL complexes contained excess cholesterol but no relationship was seen between atherosclerosis and number of LDL complexed. In animals with LDL between 3.6 x 10(6) and 4.8 x 10(6) daltons, considerable variability in PG binding was apparent, but this also was not related to LDL chemical composition. In this group of pigeons, which were all White Carneau, the positive relationship of PG-LDL binding and aorta cholesterol concentration was significant (r = 0.67, P less than 0.05). These results suggest that factors other than chemical composition (perhaps surface charge or apoprotein conformation changes) influence PG-LDL binding and that the assessment of PG-LDL binding is useful in predicting atherosclerosis in animals that do not respond to hypercholesterolemia by increasing LDL size.
Atherosclerosis 1989 Jan
PMID:Low density lipoprotein interaction with artery derived proteoglycan: the influence of LDL particle size and the relationship to atherosclerosis susceptibility. 293 Jun 13

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

Although the selective interaction of low density lipoproteins (LDL) with arterial proteoglycans is known, information is lacking on LDL-binding affinity of different subspecies occurring within a proteoglycan family. Isomeric chondroitin sulfate proteoglycan preparations sedimenting at densities of 1.54 g/ml (D1), 1.50 g/ml (D2) and 1.46 g/ml (D3) were isolated from bovine aorta intima-media under dissociative conditions and subjected to equilibrium binding to LDL-agarose gel. D1, D2 and D3 contained 36%, 37% and 11% dermatan sulfate, respectively. Sulfate to hexosamine ratio was low (0.73) in D1 when compared to D2 and D3 (0.94 and 1.04). Of the total proteoglycans contained in D1, D2 and D3, 41%, 52% and 66% interacted with LDL, respectively. LDL-bound proteoglycans dissociated over a wide range of ionic strengths (0.15-1.0); in comparison, LDL-bound heparin dissociated within a narrow range (0.5-0.75). Unlike other preparations, 30% of bound D3 dissociated at an ionic strength of 1.0. In D1 and D2 the proportion of dermatan sulfate increased in proteoglycan fractions that were bound firmly to LDL, whereas a high affinity fraction in D3 contained no dermatan sulfate. Thus, isomeric chondroitin sulfate proteoglycans display considerable divergence with respect to LDL binding. This may depend not only on the degree of sulfation but on other characteristics of the chondroitin sulfate isomers as well.
Atherosclerosis 1988 Jul
PMID:Low density lipoprotein binding affinity of arterial wall isomeric chondroitin sulfate proteoglycans. 321 55

The synthesis of proteoglycans by aorta explants from rabbits with diet-induced atherosclerosis and controls was studied by 35S-incorporation. Proteoglycans were isolated under dissociative conditions from incubation medium and from arterial explants. Additionally, the tissue proteoglycans that were not extracted by 4 M guanidine-HCl were solubilized by digestion of the tissue by elastase in the presence of proteinase inhibitors. The residual tissue was hydrolyzed by papain and glycosaminoglycans were isolated. The atherosclerotic aorta tissue incorporated twice the amount of 35S into proteoglycans than observed for controls; in both groups about 70% of the label incorporated into the tissue was noted in the proteoglycans extracted by guanidine-HC;, while about 30% of the total 35S-labeled proteoglycans synthesized by the explants were found in the media. Atherosclerotic tissue incorporated 35S predominantly into chondroitin sulfate proteoglycans when compared to control tissue. The chondroitinase ABC-digestable proteoglycans that were extracted by guanidine-HCl from atherosclerotic tissues were of larger molecular size than those from control tissue, but the core proteins from these preparations were similar. The heparan sulfate proteoglycan that was obtained by dissociative extraction from atherosclerotic tissue had greater amounts of N-acetyl and lesser amounts of N-sulfate ester groups than the preparation from control tissue. Digestion of the tissue by elastase yielded heparan sulfate proteoglycan as the major constituent in both groups, although atherosclerotic tissue contained relatively small amounts of this proteoglycan. The residual tissue from both groups contained chondroitin sulfate and heparan sulfate as the major glycosaminoglycans with the latter showing a decrease with atherosclerosis. Atherosclerotic tissue secreted into the medium about two-fold more 35S-labeled proteoglycans with larger molecular size than control tissue; proteoglycans of the heparan sulfate and chondroitin sulfate types were the major constituents in the culture medium of both tissues. Thus, proteoglycans undergo both quantitative and qualitative changes in atherosclerosis, reflecting the enhanced smooth muscle cell activity. These changes are potentially important in modulating lipoprotein binding and hemostatic properties, as well as fibrillogenesis of the arterial wall.
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PMID:Composition of proteoglycans synthesized by rabbit aortic explants in culture and the effect of experimental atherosclerosis. 334 58

Myo-intimal proteoglycan metabolism is thought to be important in blood vessel homeostasis, blood clotting, atherogenesis, and atherosclerosis. Human platelet-derived transforming growth factor type beta (TGF-beta) specifically stimulated synthesis of at least two types of chondroitin sulfate proteoglycans in nonproliferating human adult arterial smooth muscle cells in culture. Stimulation of smooth muscle cell proteoglycan synthesis by smooth muscle cell growth promoters (epidermal growth factor, platelet-derived growth factor, and heparin-binding growth factors) was less than 20% of that elicited by TGF-beta. TGF-beta neither significantly stimulated proliferation of quiescent smooth muscle cells nor inhibited proliferating cells. The extent of TGF-beta stimulation of smooth muscle cell proteoglycan synthesis was similar in both nonproliferating and growth-stimulated cells. TGF-beta, which is a reversible inhibitor of endothelial cell proliferation, had no comparable effect on endothelial cell proteoglycan synthesis. These results are consistent with the hypothesis that TGF-beta is a cell-type-specific regulator of proteoglycan synthesis in human blood vessels and may contribute to the myo-intimal accumulation of proteoglycan in atherosclerotic lesions.
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PMID:Transforming growth factor type beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells. 347 55

Proteoglycans accumulate in the intimal layer of blood vessels during the early stages of atherosclerosis and predispose the vessel wall to further complications of this disease. Arterial endothelial and smooth muscle cell cultures have been used to study the metabolism of vessel wall proteoglycans in an attempt to determine whether cellular events associated with the genesis of this disease, such as cellular proliferation, ageing, migration and interaction with components of the extracellular matrix, influence the metabolism of arterial proteoglycans. Proteoglycan analyses of vascular cells reveal that endothelial cells synthesize multiple species of heparan sulphate proteoglycan while smooth muscle cells synthesize little heparan sulphate proteoglycan but significant quantities of chondroitin and dermatan sulphate proteoglycan. Each family of proteoglycans synthesized by each cell type differs with regard to charge density, hydrodynamic size, glycosaminoglycan type and size, oligosaccharide content and ability to form high molecular weight aggregates. A monoclonal antibody has been generated against the chondroitin sulphate proteoglycan and used to immunolocalize this antigen to the interstitial matrix of normal and diseased blood vessels. Experiments are presented to indicate that proteoglycan metabolism is modulated when cultured arterial cells are stimulated to proliferate and migrate. Other factors shown to influence proteoglycan metabolism include the age of the cell and the nature of the substratum upon which the cells are grown. These culture systems provide useful models with which to study the factors involved in the regulation of proteoglycan synthesis by vascular cells.
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PMID:Vascular cell proteoglycans: evidence for metabolic modulation. 381 18

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


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