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Biomedical subjects

B Radhakrishnamurthy

Publications and source records attributed to B Radhakrishnamurthy.

At least 37 records · Page 2Linked to original sources
PubMed1992

Lipoprotein-proteoglycan complexes from atherosclerotic lesions promote cholesteryl ester accumulation in human monocytes/macrophages.

Lipoprotein-proteoglycan complexes from human atherosclerotic lesions were studied to determine their ability to stimulate cholesteryl ester accumulation in human monocytes/macrophages. Complexes containing apolipoprotein (apo) B lipoproteins and proteoglycans were extracted from fatty streaks and fibrous plaque lesions of human aortas by extraction with 0.15 M NaCl. Fractionation of the complex with Bio-Gel A-50m yielded a single fraction from fatty streaks and two fractions from fibrous plaques. The complexes were further purified by anti-apo B affinity chromatography and analyzed for apolipoproteins, lipids, and glycosaminoglycans Apo B was the only apolipoprotein present in the complexes. Although the complexes from fatty streaks and fibrous plaques contained varying proportions of hyaluronic acid, chondroitin 6-sulfate, and dermatan sulfate, heparin was present in only the fibrous plaque complexes. All three lipoprotein-proteoglycan complexes increased the rate of incorporation of [14C]oleate into cholesteryl [14C]oleate and stimulated cholesteryl ester accumulation in monocytes/macrophages. However, the complexes from fibrous plaques were more potent than those from fatty streaks in this regard. Cholesteryl ester synthesis that is mediated by the uptake of the complexes was dose dependent and showed apparent saturation, suggesting that cell surface binding may be required. Chloroquine, a lysosomotropic agent, inhibited cholesteryl ester synthesis that is induced by the complexes, indicating that lysosomal hydrolysis was essential. Cholesteryl ester synthesis that is mediated by the complexes was inhibited 70-79% by polyinosinic acid. Furthermore, excess unlabeled fibrous plaque complexes significantly inhibited the binding and internalization of in vitro 125I-low density lipoprotein (LDL)-proteoglycan complexes and 125I-acetylated-LDL and not 125I-LDL. These results suggest the involvement of the scavenger receptor in the uptake of the complexes. Phagocytosis played a minor role in the metabolism of these ligands because cytochalasin D inhibited cholesteryl ester synthesis, which is mediated by fibrous plaque complexes, by 7.5-25%. Cholesteryl ester synthesis increased linearly over 32 hours in macrophages incubated with the complexes, indicating an apparent lack of downregulation of binding sites. This resulted in the appearance of intracellular oil red O-positive lipid droplets. These studies show for the first time that apo B lipoprotein-proteoglycan complexes isolated from human atherosclerotic lesions can induce cholesteryl ester accumulation in monocytes/macrophages.

Arteriosclerosis↗
PubMed1991

Studies on the mechanism of uptake of low density lipoprotein-proteoglycan complex in macrophages.

Earlier, we (Vijayagopal, P. et al. (1988) Biochim. Biophys. Acta 960, 210) showed that mouse peritoneal macrophages metabolize low density lipoprotein (LDL)-proteoglycan complex by a receptor pathway distinct from the acetyl-LDL receptor. Further studies were conducted to probe further into the mechanism of LDL-proteoglycan complex uptake by macrophages. Both 125I-methyl-LDL-proteoglycan complex and 125I-LDL-proteoglycan complex were taken up and degraded by the cells to the same extent. Similarly, the ability of these ligands to stimulate cholesteryl ester synthesis was also indistinguishable. These results rule out the possibility of apoB,E receptor involvement in the uptake of LDL-proteoglycan complex in macrophages. Sodium fluoride, cytochalasin D and aggregated LDL inhibited degradation of the complex by 24%, 26% and 28%, respectively, indicating that phagocytosis is only a minor pathway for the uptake. Both binding and degradation of the complex were not inhibited by excess hyaluronic acid suggesting that ligand recognition was not through hyaluronic acid binding sites. As compared to acetyl-LDL, the cellular degradation of LDL-proteoglycan complex was retarded. Macrophages exhibited a rapid stimulation of [3H]inositol trisphosphate (IP3) release and diacylglycerol production when incubated with LDL-proteoglycan complex. Furthermore, pertussis toxin produced a 62% inhibition of LDL-proteoglycan complex mediated IP3 release, suggesting that LDL-proteoglycan complex metabolism in macrophages is dependent upon the G-protein coupled signal transduction mechanism. These results show that receptor mediated endocytosis plays a major role in the metabolism of LDL-proteoglycan complex in macrophages.

Animals↗
PubMed1991

Interaction of a high-affinity heparin subfraction with low-density lipoprotein stimulates cholesteryl ester accumulation in mouse macrophages.

A high-affinity heparin subfraction accounting for 8% of whole heparin from bovine lung was isolated by low-density lipoprotein (LDL)-affinity chromatography. When compared to whole heparin, the high-affinity subfraction was relatively higher in molecular weight (11,000 vs. 17,000) and contained more iduronyl sulfate as hexuronic acid (76% vs. 86%), N-sulfate ester (0.75 vs. 0.96 mol/mol hexosamine), and O-sulfate ester (1.51 vs. 1.68 mol/mol hexosamine). Although both heparin preparations formed insoluble complexes with LDL quantitatively in the presence of 30 mM Ca2+, the concentrations of NaCl required for 50% reduction in maximal insoluble complex formation was markedly higher with high-affinity subfraction (0.55 M vs. 0.04 M). When compared to complex of 125I-LDL and whole heparin (H-125I-LDL), complex of 125I-LDL and high-affinity heparin subfraction (HAH-125I-LDL) produced marked increase in the degradation of lipoproteins by macrophages (7-fold vs. 1.4-fold over native LDL, after 5 h incubation) as well as cellular cholesteryl ester synthesis (16.7-fold vs. 2.2-fold over native LDL, after 18 h incubation) and content (36-fold vs. 2.7-fold over native LDL, after 48 h incubation). After a 5 h incubation, macrophages accumulated 2.3-fold more cell-associated radioactivity from HAH-125I-LDL complex than from [125I]acetyl-LDL. While unlabeled HAH-LDL complex produced a dose-dependent inhibition of the degradation of labeled complex, native unlabeled LDL did not elicit any effect even at a 20-fold excess concentration. Unlabeled particulate LDL aggregate competed for 33% of degradation of labeled complex; however, cytochalasin D, known inhibitor of phagocytosis, did not effectively inhibit the degradation of labeled complex. Unlabeled acetyl-LDL produced a partial (33%) inhibition of the degradation of labeled complex. These results indicate that (1) the interaction of high-affinity heparin subfraction with LDL leads to scavenger receptor mediated endocytosis of the lipoprotein, and stimulation of cholesteryl ester synthesis and accumulation in the macrophages; and (2) with respect to macrophage recognition and uptake, HAH-LDL complex was similar but not identical to acetyl-LDL. These observations may have implications for atherogenesis, because both mast cells and endothelial cells can synthesize heparin in the arterial wall.

Animals↗
PubMed1991

Proteoglycans, lipoproteins, and atherosclerosis.

The arterial wall proteoglycans play a crucial role in the pathogenesis of atherosclerosis as depicted schematically in Figure 7. Plasma components including lipoproteins cross the endothelium mainly by a non-specific bulk-phase vesicular transport. A selective interaction of apoB-containing lipoproteins occurs with proteoglycans of the subendothelial layer which results in extracellular retention and accumulation of lipoproteins. Such interaction alters the structural and charge characteristics of LDL particles. These altered LDL are taken up by monocyte-derived macrophages by scavenger receptor-mediated endocytosis, leading to cholesteryl ester accumulation and foam cell formation. Further, retention of LDL by proteoglycans in the extracellular matrix also increases the chances of oxidative modification of lipoproteins. All of these changes may be occurring at a marginal level as a normal adaptive process of the arterial wall. However, focal response to chronic hemodynamic stress, hyperlipidemia or other forms of injury may functionally alter the endothelium, and cause greater influx of lipoproteins and smooth muscle cell proliferation, resulting in increased synthesis of proteoglycans with altered characteristics. Enhanced binding of apo-B containing lipoproteins to proteoglycans under these conditions sets the stage for the development of athersclerosis.

Animals↗
PubMed1990

Factors regulating the metabolism of low-density lipoprotein-proteoglycan complex in macrophages.

We studied the factors regulating the metabolism of low-density lipoprotein (LDL)-proteoglycan complex, LDL and acetyl-LDL in mouse peritoneal macrophages. Macrophage conditioned medium stimulated the degradation of LDL-proteoglycan complex and acetyl-LDL in a dose-dependent manner and enhanced cholesteryl ester synthesis mediated by these ligands. The conditioned medium had no such effect in a cell-free system. The conditioned medium enhanced the degradation of both the LDL and proteoglycan components of the complex. The degradation of LDL was not affected by the conditioned medium. The active factor in the conditioned medium was labile to boiling, suggesting that it may be protein in nature. The conditioned medium also lost its stimulatory activity after dialysis through a membrane with an exclusion limit of 25,000 daltons, suggesting the involvement of cytokines and/or other growth factors. Macrophage activation was accompanied by a 2-3-fold increase in the degradation of LDL-proteoglycan complex and acetyl-LDL as compared to the degradation of these ligands in resident macrophages; however, this had no effect on LDL degradation. The degradation of all three ligands increased markedly with decreasing cell density. Preincubation of macrophages for 48 h with increasing concentrations of fetal bovine serum produced a substantial increase in the subsequent degradation of LDL-proteoglycan complex and acetyl-LDL, while it had very little effect on the degradation of LDL. The active factor in serum was destroyed by boiling, suggesting that it may be a protein. These results show that the scavenger receptor, mediating the uptake and degradation of LDL-proteoglycan complex and acetyl-LDL and LDL receptor are regulated differently in mouse peritoneal macrophages.

Animals↗
PubMed1990

Arterial wall proteoglycans--biological properties related to pathogenesis of atherosclerosis.

The arterial wall is a complex organ system with respect to carbohydrate-protein macromolecules, particularly proteoglycans. Proteoglycans in the arterial wall display polydispersity and heterogeneity even in the same family. At least two major types are known: chondroitin sulphate-dermatan sulphate type and heparan sulphate type. These proteoglycans have varied biological properties, and some of these properties are implicated in the development of atherosclerosis. The chondroitin sulphate-dermatan sulphate proteoglycans are capable of forming complexes with serum low-density lipoproteins, a process conductive to lipid accumulation in the extracellular space of the arterial wall. Also, such reactions render low-density lipoprotein particles electronegative aggregates. These altered low-density lipoproteins are taken up by macrophages (and possibly by proliferative smooth muscle cells) through a high-affinity receptor pathway devoid of feedback regulation, which results in intracellular lipid accumulation and foam-cell formation, a hallmark of atherosclerosis. On the other hand, heparan sulphate proteoglycan located on the cell surface and internal elastic lamina is antithrombogenic, and facilitates binding of the lipid-clearing enzyme, lipoprotein lipase, to endothelium. Thus, chondroitin sulphate and heparan sulphate proteoglycans with divergent biological properties play a crucial role in the pathogenesis of atherosclerosis.

Animals↗
PubMed1989

Low-density lipoprotein binding affinity of arterial wall proteoglycans: characteristics of a chondroitin sulfate proteoglycan subfraction.

The characteristics of an arterial wall chondroitin sulfate proteoglycan (CS-PG) subfraction that binds avidly to low-density lipoproteins (LDL) was studied. A large CS-PG was extracted from bovine aorta intima-media under dissociative conditions, purified by density-gradient centrifugation and gel filtration chromatography, and further subfractionated by affinity chromatography on LDL-agarose. A proteoglycan subfraction, representing 25% of the CS-PG, showed an elution profile (with dissociation from LDL-agarose occurring between 0.5 and 1.0 M NaCl) corresponding to that of heparin, heretofore considered to be the most strongly binding glycosaminoglycan with LDL. The proteoglycan subfraction which migrated as a single band on composite agarose-polyacrylamide gel electrophoresis contained chondroitin 6-sulfate, chondroitin 4-sulfate and dermatan sulfate in a proportion of 70:22:8. The core protein of the proteoglycan had an apparent molecular weight of 245,000, and contained approx. 33 glycosaminoglycan chains with an average molecular weight of 32,000. The CS-PG subfraction, like heparin, formed insoluble complexes in the presence of 30 mM Ca2+. Complexing of LDL with proteoglycan resulted in two classes of interactions with 0.1 and 0.3 proteoglycan monomer bound per LDL particle characterized by an apparent Kd of 4 and 21 nM, respectively. This indicates that multiple LDL particles bind to single proteoglycan monomers even at saturation. In contrast, LDL-heparin interactions showed a major component characterized by an apparent Kd of 151 nM and a Bmax of 9 heparin molecules per LDL particle. The occurrence of a potent LDL-binding proteoglycan subfraction within the family of arterial CS-PG may be of importance in terms of lipid accumulation in atherogenesis.

Amino Acids↗
PubMed1989

Composition of proteoglycans in the aortas of copper-deficient rats.

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.

Animals↗
PubMed1988

Effect of low-density lipoproteins on the synthesis and secretion of proteoglycans by human endothelial cells in culture.

We studied the effect of low-density lipoproteins (LDL) on the synthesis and secretion of proteoglycans by cultured human umbilical-vein endothelial cells. Confluent cultures were incubated with [35S]sulphate or [3H]glucosamine in lipoprotein-deficient serum in the presence and in the absence (control) of LDL (100-400 micrograms/ml), and metabolically labelled proteoglycans in culture medium and cell layer were analysed. LDL increased accumulation of labelled proteoglycans in medium and cell fractions up to a concentration of 200 micrograms/ml. At this concentration of LDL the accumulations of proteoglycans in medium and cell layer were 65% and 32% respectively above control for 35S-labelled proteoglycans, and 55% and 28% respectively above control for 3H-labelled proteoglycans. At concentrations above this LDL was found to depress the accumulation of proteoglycans in medium and cell layer. Gel filtration on Sepharose CL-4B showed that in both control and LDL-treated cultures the cell layer contained a large (Kav. = 0) and a small (Kav. = 0.35) heparan sulphate proteoglycan, whereas the culture medium contained a large heparan sulphate proteoglycan (Kav. = 0) and a smaller isomeric chondroitin sulphate proteoglycan (control, Kav. = 0.35; LDL-treated, Kav. = 0.17). The relative increase in hydrodynamic size of the isomeric chondroitin sulphate proteoglycan (Mr 150,000 compared with 90,000) in the medium of cultures exposed to LDL was partly attributable to the larger size of the glycosaminoglycan side chains (Mr 39,000 compared with 21,000). The isomeric chondroitin sulphate proteoglycan in LDL-treated culture was relatively enriched in chondroitin 6-sulphate compared with that in control cultures (39% compared with 29%). Pulse-chase studies showed that LDL treatment did not alter the turnover rate of proteoglycans as compared with controls, implying that the elevation in proteoglycan accumulation in LDL-treated cultures was due to enhanced synthesis. These results demonstrate that LDL can modulate proteoglycan synthesis by cultured vascular endothelial cells, resulting in the secretion of a larger isomeric chondroitin sulphate proteoglycan enriched in chondroitin 6-sulphate.

Cells, Cultured↗
PubMed1988

Activation of dolichol-phosphate mannosyltransferase by dibutryl cyclic AMP in rat liver.

Radiolabeled mannose incorporation into secretory glycoproteins and immunoprecipitable fibronectin in the incubation media significantly increased (105 and 32 percent respectively) with a corresponding increase in the levels of dolichol-phosphate mannose, dolichol-diphosphate oligosaccharides and dolichol-phosphate mannosyltransferase activity in the rat liver slices when incubated with dibutryl cAMP and ATP. Dibutryl cAMP activated maximally this enzyme in the presence of ATP in the incubation medium. The activation of the enzyme resulted in a two fold increase in Vmax with no apparent change in the Km for GDP mannose. Phosphorylation the rat liver microsomes with catalytic subunit of cAMP dependent protein kinase, resulted in the activation of dolichol-phosphate mannosyltransferase. These results suggest that cAMP modulates protein glycosylation by activating dolicholphosphate mannosyltransferase activity. The activation of this enzyme could be through phosphorylation/dephosphorylation mechanism involving a cAMP dependent protein kinase.

Adenosine Triphosphate↗
PubMed1988

Metabolism of low-density lipoprotein-proteoglycan complex by macrophages: further evidence for a receptor pathway.

Earlier, we (Vijayagopal, P., et al. (1985) Biochim. Biophys. Acta 837-251) have shown that complexes of plasma low-density lipoproteins (LDL) and arterial chondroitin sulfate-dermatan sulfate proteoglycan aggregate promote LDL degradation and cholesteryl ester accumulation in mouse peritoneal macrophages. Further studies were conducted to determine whether LDL-proteoglycan complex is metabolized by a receptor-mediated process. Native proteoglycan aggregate was isolated from bovine aorta by associative CsCl isopycnic centrifugation. Complex of 125I-labeled LDL and proteoglycan aggregate formed in the presence of 30 mM Ca2+ was incubated with macrophages, and the binding at 4 degrees C and degradation at 37 degrees C of 125I-labeled LDL in the complex was monitored. Both binding and degradation of the complex were specific and saturable, suggesting that the processes are receptor mediated. The Kd for binding was 23 micrograms LDL protein per ml in the complex. Degradation of 125I-labeled LDL-proteoglycan complex was not suppressed by preincubation of macrophages with excess unlabeled complex, suggesting that the receptor for the complex is not subject to down regulation. Both binding and degradation of the complex and the resultant stimulation of cholesteryl ester synthesis were inhibited by limited treatment of cells with low doses of trypsin and pronase, indicating that the binding sites are protein or glycoprotein in nature. Binding was not inhibited by an excess of native LDL and beta-VLDL and exhibited only partial competition by excess unlabeled acetyl-LDL; however, polyinosinic acid, fucoidin and dextran sulfate, known inhibitors of acetyl-LDL binding and degradation in macrophages, did not affect LDL-proteoglycan complex binding and degradation. Similarly, excess unlabeled LDL-proteoglycan complex produced only partial inhibition of the binding and degradation of 125I-labeled acetyl-LDL by macrophages, suggesting that the binding sites for acetyl-LDL and LDL-proteoglycan complex are probably not identical. These studies provide evidence for a receptor-mediated pathway for the metabolism of LDL-proteoglycan complex in macrophages.

Animals↗
PubMed1988

Composition of proteoglycans synthesized by rabbit aortic explants in culture and the effect of experimental atherosclerosis.

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.

Animals↗
PubMed1988

Low density lipoprotein binding affinity of arterial wall isomeric chondroitin sulfate proteoglycans.

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.

Animals↗
PubMed1988

Influence of partial replacement of starch by sucrose in high fat-cholesterol diet on serum lipoprotein responses of cynomolgus monkeys.

The influence of partial replacement of starch by sucrose on dietary cholesterol-induced serum lipoprotein responses was examined in 10 male cynomolgus monkeys (Macaca fascicularis). In a crossover design two semipurified diets provided either starch or starch and sucrose (1:1) as carbohydrate (49% by calories) with 0.4 mg cholesterol/kcal. Six weeks of starch + sucrose diet resulted in significantly reduced levels (mean +/- SE, mg/dl) of serum total cholesterol (264 +/- 9 vs 244 +/- 8) and apo B (110 +/- 6 vs 96 +/- 6) when compared with starch diet, whereas serum triglyceride levels remained similar between diets. With respect to changes in lipids and apolipoproteins (A-I or B) of very low (VLDL), low (LDL), intermediate (IDL), and high (HDL) density lipoproteins, starch + sucrose diet significantly increased VLDL-apo B (+34%), and decreased LDL-cholesterol (-18%) and LDL-apo B (-15%) as compared with starch alone; no differences were found in IDL and HDL between diets. The relative proportion of starch to sucrose in a diet appears to influence the magnitude of response of lipoproteins to dietary cholesterol.

Animals↗
PubMed1988

Arterial wall injury and proteoglycan changes in atherosclerosis.

The concept of injury as a mechanism leading to atherosclerosis has been fostered by numerous studies of initiating factors and by observation of the response of cardiovascular connective tissue, ie, cellular and extracellular matrix components. Carbohydrate-protein macromolecules of the extracellular matrix are a complex group of biologically important substances that play a crucial role in mesenchymal tissue repair following injury, a process needed to maintain arterial wall integrity. Of particular interest are the proteoglycans that enter into a variety of roles, from that of inhibiting atherosclerosis and helping to maintain fibrillar structures to that of taking part in lipid deposition in the development of atherosclerosis.

Animals↗
PubMed1987

Composition of proteoglycans from human atherosclerotic lesions.

Proteoglycans from human atherosclerotic lesions and from uninvolved aortic intima were isolated and their composition was studied. The tissues were sequentially extracted by guanidine hydrochloride followed by hydrolysis of the tissue by elastase. Chondroitin sulfate/dermatan sulfate proteoglycans were predominant in guanidine hydrochloride extracts of the tissue. Most of the heparan sulfate proteoglycans were released from the tissue by hydrolysis with elastase. The content of proteoglycan material, measured as uronate per unit weight of wet tissue, was lower in fatty streaks and fibrous plaques than in uninvolved tissue (0.58 and 0.48 mg vs. 0.7 mg/g wet tissue). The distribution of different glycosaminoglycans in guanidine hydrochloride-extracted proteoglycans was similar among the lesions and uninvolved tissue, but varied in the elastase-hydrolyzed extracts. Gel filtration studies suggested that the major proteoglycan material, chondroitin sulfate proteoglycans, from lesions had greater molecular weight than proteoglycans from uninvolved tissue. The studies indicate that alteration in intrinsic composition and molecular size of proteoglycans occurs in atherosclerotic lesions.

Aorta↗
PubMed1987

Dietary carbohydrate type and cholesterol-induced hypercholesterolemia in cynomolgus monkeys: influence of oral antibiotic.

The relationship of carbohydrate type to cholesterol-induced hypercholesterolemia and the potential role of intestinal flora in the above process were examined in 12 male cynomolgus monkeys (M. fascicularis). Semipurified diets provided two types of carbohydrates (starch or sucrose, 49% by calorie) with 0.4 mg cholesterol/kcal. Six weeks of the starch diet resulted in significantly enhanced hypercholesterolemia when compared to sucrose diet. Starch in relation to sucrose produced cholesterol enrichment of intermediate density lipoproteins and increase in low density lipoprotein particles, whereas sucrose increased high density lipoprotein constituents (phospholipids, cholesterol, and apoA-I) and triglyceride content of very low density lipoproteins. Fecal Escherichia counts were high during the starch diet as contrasted with sucrose diet, but the Escherichia, Streptococcus, and Bacteroides groups did not show differences by diet following each consecutive 4-week period of oral neomycin (107 mg/kg body wt) treatment and withdrawal. The magnitude of hypercholesterolemia during these periods also remained similar between starch and sucrose, suggesting formation of germfree metabolic characteristics. Thus, the magnitude of cholesterol-induced hypercholesterolemia can be affected by the type of carbohydrate, which may be in part determined by intestinal flora metabolism.

Animals↗