heparitin-sulfate and Arteriosclerosis

Thromboembolic vascular diseases remain the main cause of death in Western industrialized societies. Anticoagulants retard the formation, growth, and embolization of thrombi and are effective agents in the prevention and treatment of thromboembolic disease. Anticoagulants in venous thromboembolism have been investigated extensively with rigorous randomized, controlled trials, while the roles for anticoagulants in arterial thromboembolism generally have evolved through natural history studies and empirical practice. Thus, many current guidelines for anticoagulant use in arterial disease are based on successful established routines and rational therapy. To effectively balance the efficacy and risks of anticoagulation, the vascular surgeon needs a thorough understanding of anticoagulant drugs, their mechanisms of action, and their proven and unproven indications. Since the first use of heparin in arterial surgery, a variety of new and different anticoagulants have become available, including low-molecular-weight heparins, heparin-like drugs, hirudins, and thrombin inhibitors. Despite their diverse actions, they all inhibit some portion of the plasma coagulation cascade, thus distinguishing them from platelet inhibitors or fibrinolytics. Every interference with the coagulation cascade carries a risk of minor, major, or fatal hemorrhage. To date, no drug or therapeutic strategy has succeeded fully in dissociating its antithrombotic effects from its risks of bleeding.

Topics: Anticoagulants; Arteriosclerosis; Blood Coagulation; Chondroitin Sulfates; Coumarins; Dermatan Sulfate; Drug Combinations; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Platelet Activation; Thrombin; Thromboembolism

Topics: Animals; Arteriosclerosis; Cell Division; Cell Movement; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Muscle, Smooth, Vascular; Proteoglycans; Rabbits; Tunica Intima

Topics: Animals; Arteriosclerosis; Cations; Cell Division; Heparin; Heparitin Sulfate; Humans; Muscle, Smooth, Vascular; Structure-Activity Relationship

1. Heparan sulfate proteoglycan in the basal lamina of smooth muscle cells is important in the maintenance of the 'contractile', high volume fraction of myofilaments (Vvmyo) phenotype. The mechanism by which this occurs may involve the continuous internalization of heparan sulfate by the smooth muscle cells themselves. 2. One macrophage can degrade all the heparan sulfate from three smooth muscle cells by the action of heparan sulfate-degrading enzymes in their lysosomes, thus leaving none available for internalization by the smooth muscle cell until it has synthesized more, and leading to the induction of smooth muscle phenotypic change from a high Vvmyo to a low Vvmyo. 3. In this altered phenotype the smooth muscle cells proliferate in response to mitogens, synthesize large amounts of extracellular matrix and accumulate lipid, all characteristics of the smooth muscle cell in developing atheroma.

Topics: Actin Cytoskeleton; Animals; Arteriosclerosis; Cell Communication; Heparitin Sulfate; Humans; In Vitro Techniques; Macrophages; Muscle, Smooth, Vascular; Phenotype

Topics: Animals; Antithrombin III; Arteriosclerosis; Cell Division; Endothelium, Vascular; Glycosaminoglycans; Heparin; Heparitin Sulfate; Molecular Structure; Muscle, Smooth, Vascular; Structure-Activity Relationship; Sulfates

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.

Topics: Animals; Arteries; Arteriosclerosis; Chondroitin Sulfate Proteoglycans; Connective Tissue; Dermatan Sulfate; Endothelium; Glycosaminoglycans; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Muscle, Smooth, Vascular; Proteoglycans

Topics: Animals; Aorta; Arteriosclerosis; Cattle; Cell Division; Culture Media; Endothelium; Glycosaminoglycans; Heparin; Heparitin Sulfate; In Vitro Techniques; Muscle, Smooth, Vascular; Rats

Topics: Arteries; Arteriosclerosis; Chemical Phenomena; Chemistry, Physical; Chondroitin; Collagen; Connective Tissue; Glycosaminoglycans; Heparitin Sulfate; Humans; In Vitro Techniques; Lipoproteins

Topics: Adult; Animals; Arteries; Arteriosclerosis; Blood Coagulation; Chondroitin; Collagen; Elastic Tissue; Elastin; Female; Glycoproteins; Glycosaminoglycans; Heparitin Sulfate; Humans; Lipid Metabolism; Lipids; Lipoproteins; Rabbits; Staining and Labeling; Veins

Topics: Aging; Animals; Arteriosclerosis; Ascorbic Acid; Chondroitin; Connective Tissue; Coronary Disease; Diet, Atherogenic; Glycoproteins; Glycosaminoglycans; Heparin; Heparitin Sulfate; Hexosamines; Hexoses; Histamine; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Lipid Metabolism; Lipoproteins, LDL; Mucoproteins; Neuraminic Acids; Rabbits; Rats

The etiology of ischemic stroke affects prognosis, outcome, and management. Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke. A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST).. A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies. "Possible" and "probable" diagnoses can be made based on the physician's certainty of diagnosis. The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria. The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients, first based only on clinical features and then after reviewing the results of diagnostic tests.. The TOAST classification denotes five subtypes of ischemic stroke: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) stroke of other determined etiology, and 5) stroke of undetermined etiology. Using this rating system, interphysician agreement was very high. The two physicians disagreed in only one patient. They were both able to reach a specific etiologic diagnosis in 11 patients, whereas the cause of stroke was not determined in nine.. The TOAST stroke subtype classification system is easy to use and has good interobserver agreement. This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke. Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke.

Topics: Anticoagulants; Arteriosclerosis; Brain Ischemia; Cerebral Infarction; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Embolism; Glycosaminoglycans; Heparinoids; Heparitin Sulfate; Humans

Syndecans are transmembranous heparan sulfate proteoglycans abundant in the surface of all adherent mammalian cells and involved in vital cellular functions. In this study, we found syndecan-1, -2, -3, and -4 to be constitutively expressed by human umbilical vein endothelial cells. The exposure of the ectodomains of syndecan-1 and -4 to the cell surface and their constitutive shedding into the extracellular compartment was measured by immunoassays. In the presence of plasmin and thrombin, shedding was accelerated and monitored by detection and identification of (35)S-labeled proteoglycans. To elucidate the cleavage site of the syndecan ectodomains, we used a cell-free in vitro system with enzyme and substrate as the only reactants. For this purpose, we constructed recombinant fusion proteins of the syndecan-1 and -4 ectodomain together with maltose-binding protein and enhanced yellow fluorescent protein as reporter proteins attached to the N and C termini via oligopeptide linkers. After protease treatment of the fusion proteins, the electrophoretically resolved split products were sequenced and cleavage sites of the ectodomain were identified. Plasmin generated cleavage sites at Lys(114) downward arrowArg(115) and Lys(129) downward arrowVal(130) in the ectodomain of syndecan-4. In thrombin proteolysates of the syndecan-4 ectodomain, the cleavage site Lys(114) downward arrowArg(115) was also identified. The cleavage sites for plasmin and thrombin within the syndecan-4 ectodomain were not present in the syndecan-1 ectodomain. Cleavage of the syndecan-1 fusion protein by thrombin occurred only at a control cleavage site (Arg downward arrowGly) introduced into the linker region connecting the ectodomain with the enhanced yellow fluorescent protein. Because both plasmin and thrombin are involved in thrombogenic and thrombolytic processes in the course of the pathogenesis of arteriosclerosis, the detachment of heparan sulfate-bearing ectodomains could be relevant for the development of arteriosclerotic plaques and recruitment of mononuclear blood cells to the plaque.

Topics: Amino Acid Sequence; Arginine; Arteriosclerosis; Bacterial Proteins; Binding Sites; Carrier Proteins; Cell-Free System; DNA, Complementary; Endothelium, Vascular; Fibrinolysin; Heparitin Sulfate; Humans; Immunoassay; Kinetics; Luminescent Proteins; Lysine; Maltose-Binding Proteins; Membrane Glycoproteins; Molecular Sequence Data; Oligopeptides; Peptide Hydrolases; Polymerase Chain Reaction; Protein Structure, Tertiary; Proteoglycans; Syndecan-1; Syndecan-4; Syndecans; Thrombin; Time Factors; Umbilical Veins; Valine

Aggregated low-density lipoprotein (LDL) was shown to be present in the atherosclerotic lesion, but the mechanism responsible for its formation in vivo is not known yet. To find out whether LDL aggregation occurs in the arterial wall during atherogenesis, LDLs were extracted from the aortas of apolipoprotein E-deficient (E(0)) mice during their aging (and the development of atherosclerosis), and were analyzed for their aggregation states, in comparison to LDLs isolated from aortas of control mice. LDL isolated from aortas of E(0) mice was already aggregated at 1 month of age and its aggregation state substantially increased with age, with 3-fold elevation at 6 months of age compared to younger, 1-month-old, mice. Only minimal aggregation could be detected in LDL derived from control mice. Electron microscopy examination revealed that LDL particles from aortas of the E(0) mice were heterogeneous in their size, ranging between 20 and 300 nm. The mouse aortic LDL contained proteoglycans (PGs) and their content increased with the age of the mice, with about 2-fold higher levels than those found in LDLs derived from aortas of control mice. Macrophage-released PGs were previously demonstrated to enhance LDL aggregation in vitro. However, their involvement in LDL aggregation in vivo has not been studied yet. Thus, we next studied the effect of arterial macrophage-released PGs on the susceptibility of plasma LDL to aggregation by Bacillus cereus sphingomyelinase (SMase). Foam cell macrophages were isolated from aortas of the atherosclerotic E(0) mice at 6 months of age and were found to be loaded with cholesterol and to contain oxidized lipids. To analyze the effect of macrophage-released PGs on LDL aggregation, PGs were prelabeled by cell incubation with [35S]sulfate, followed by incubation of macrophage-released PGs with E(0) mouse plasma LDL (200 microg protein/ml) for 1 h at 37 degrees C. [35S]Sulfated PGs were found to be LDL-associated and the susceptibility of PG-associated LDL to aggregation by SMase was increased by up to 45% in comparison to control LDL. Similar results demonstrating the involvement of PGs in LDL aggregation were obtained upon incubation of LDL with increasing concentrations of PGs that were isolated from the entire aorta of E(o) mice (rather than the isolated macrophages). The stimulatory effect of macrophage-released PGs on LDL aggregation was markedly reduced when the PGs were pretreated with the glycosaminoglycan-hydrolyzing enzymes

Topics: Aging; Animals; Aorta; Apolipoproteins E; Arteriosclerosis; Chondroitin Sulfates; Heparitin Sulfate; Lipoproteins, LDL; Macrophages; Mice; Microscopy, Electron; Particle Size; Proteoglycans

Reduced heparin and heparan sulfate (HS) proteoglycans (PG) have been observed in both inflammation and atherosclerosis. Methods to increase endogenous heparin and heparan sulfate are not known. We found that incubation of endothelial cells with 500-1,000 micrograms/ml high density lipoprotein (HDL) increased 35SO4 incorporation into PG by 1.5-2.5-fold. A major portion of this increase was in HS and was the result of increased synthesis. Total PG core proteins were not altered by HDL; however, the ratio of 35SO4 to [3H]glucosamine was increased by HDL, suggesting increased sulfation of glycosaminoglycans. In addition, HDL increased the amount of highly sulfated heparin-like HS in the subendothelial matrix. HS from HDL-treated cells bound 40 +/- 5% more 125I-antithrombin III (requires 3-O sulfated HS) and 49 +/- 3% fewer monocytes. Moreover, the HS isolated from HDL-treated cells inhibited smooth muscle cell proliferation (by 83 +/- 5%) better than control HS (56 +/- 6%) and heparin (42 +/- 6%). HDL isolated from apolipoprotein E (apoE)-null mice did not stimulate HS production unless apoE was added. ApoE also stimulated HS production in the absence of HDL. ApoE did not increase 35SO4 incorporation in macrophages and fibroblasts, suggesting that this is an endothelial cell-specific process. Receptor-associated protein inhibited apoE-mediated stimulation of HS only at higher (20 micrograms/ml) doses, suggesting the involvement of a receptor-associated protein-sensitive pathway in mediating apoE actions. In summary, our data identify a novel mechanism by which apoE and apoE-containing HDL can be anti-atherogenic. Identification of specific apoE peptides that stimulate endothelial heparin/HS production may have important therapeutic applications.

Topics: Animals; Apolipoproteins E; Arteriosclerosis; Cattle; Cells, Cultured; Endothelium, Vascular; Glycosaminoglycans; Heparitin Sulfate; Lipoproteins, HDL; Mice; Mice, Knockout; Rats; Thrombosis

Heparan sulfate is thought to regulate the biological activities of several proteins implicated in the pathogenesis of atherosclerosis. While the interactions of heparan sulfate with lipoprotein lipase and various growth factors have been actively studied, little is known of the cellular regulation of heparan sulfate biosynthesis in response to lipid accumulation. We have investigated heparan sulfate biosynthesis during conversion of murine J774 macrophages into lipid-laden foam cells. Such conversion is shown to accelerate the rate of glycosaminoglycan synthesis and the transport of newly synthesized proteoglycans into the medium. Moreover, the structure of heparan sulfate is specifically altered due to an approximately 30% increase in the 6-O-sulfation of glucosamine residues within the N-sulfated heparan sulfate domains, whereas the sulfation of chondroitin sulfate remains unaffected. These results suggest a selective effect of foam cell conversion on the biosynthesis of heparan sulfate.

Topics: Animals; Arteriosclerosis; Cell Line; Chondroitin Sulfates; Disaccharides; Foam Cells; Glycosaminoglycans; Heparitin Sulfate; Humans; Lipoproteins, LDL; Macrophages; Mice; Nitrous Acid; Oligosaccharides

In vivo and in vitro observations strongly suggest that marked differences exist in the phenotype, growth, and matrix-producing capabilities of distinct smooth muscle cell subpopulations. An earlier study from our laboratory showed differences in matrix metalloproteinase expression patterns in cultures of medial smooth muscle cells from tissue affected by abdominal aortic aneurysm (AAA) or atherosclerotic occlusive disease and from normal arterial tissue. In this study we were interested in ascertaining whether smooth muscle cells from the same sample groups also synthesized different proteoglycan profiles that correlated with vascular disease.. Proteoglycans from smooth muscle cell monolayer cultures from tissue affected by AAA or atherosclerotic occlusive disease and from normal arterial tissue were examined by means of immunoblotting and affinity-blotting composite agarose polyacrylamide gel electrophoresis (CAPAGE) and sodium dodecyl sulphate PAGE. Enzyme-linked immunosorbent assay (ELISA) was used to quantitate perlecan levels in smooth muscle cell monolayer media samples.. Versican, perlecan, and biglycan levels were significantly elevated in AAA smooth muscle cell cultures. Two populations of smooth muscle cell versican were identified by means of CAPAGE-immunoblotting and by means of a novel affinity-blotting technique with biotinylated hyaluronan. A small keratan sulfate-substituted proteoglycan was present in similar levels in all smooth muscle cell cultures. This proteoglycan had a free core protein of about 55 kd after keratanase digestion and had a relatively high charge-to-mass ratio, as was evident from its electrophoretic mobility in CAPAGE; this proteoglycan was tentatively identified as keratocan. Immunoblotting with monoclonal antibodies 3-G-10 (anti-delta heparan sulfate, heparan sulfate stubs generated by heparitinase treatment) and 10-E-4 (anti-native heparan sulfate chains) helped identify several smooth muscle cell heparan sulfate-substituted proteoglycans. Elevated levels of intact and processed perlecan core protein were identified in AAA cultures by means of immunoblotting with a monoclonal antibody to perlecan core protein (A76). ELISA measurements confirmed that perlecan levels were significantly higher in AAA smooth muscle cell cultures compared with the normal arterial tissue and tissue affected by atherosclerotic occlusive disease.. Because heparan sulfate proteoglycans can bind growth factors, their elevated synthesis by AAA smooth muscle cells in combination with an increased expression of matrix metalloproteinases may at least partly explain the differential proliferative capacity of the AAA smooth muscle cells examined and may govern the pattern of abnormal cellular proliferation and matrix protein synthesis observed in the pathogenesis of vascular disease.

Topics: Aged; Aged, 80 and over; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Arteriosclerosis; Biglycan; Cells, Cultured; Chondroitin Sulfate Proteoglycans; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Immunoblotting; Lectins, C-Type; Middle Aged; Muscle, Smooth, Vascular; Proteoglycans; Versicans

Heparan sulfate proteoglycans produced by vascular endothelium may function physiologically to restrain the migration, multiplication, and phenotypic transition of vascular smooth-muscle cells, and to maintain an anticoagulant luminal surface by bonding and activating antithrombin III. Thus, ample production of heparan sulfate proteoglycans may act to prevent atherosclerosis and its thrombotic complications. The ability of exogenous heparin to stimulate synthesis of heparan sulfate proteoglycans by vascular endothelium may be largely responsible for the positive outcomes of most controlled evaluations of low-dose heparin as a long-term therapy for coronary disease. Glucosamine, a biosynthetic precursor of mucopolysaccharides, can substantially enhance mucopolysaccharide production when added to cultured fibroblasts or chondrocytes; the clinical utility of oral glucosamine in osteoarthritis may reflect increased synthesis of cartilage proteoglycans. It is reasonable to speculate that exogenous glucosamine will likewise enhance heparan sulfate proteoglycans production by vascular endothelial cells, and, when administered orally in regimens comparable to those effective in osteoarthritis, will thereby act to retard atherogenesis.

Topics: Animals; Arteriosclerosis; Cartilage; Cells, Cultured; Coronary Disease; Endothelium, Vascular; Fibroblasts; Glucosamine; Glycosaminoglycans; Heparan Sulfate Proteoglycans; Heparin; Heparitin Sulfate; Humans; Models, Cardiovascular; Proteoglycans

Silicon plays a physiologically essential but mechanistically obscure role in promoting the synthesis of mucopolysaccharides and collagen. In light of reports that increased silicon ingestion impedes cholesterol-induced atherogenesis in rabbits and may be associated epidemiologically with reduced cardiovascular risk, it is reasonable to speculate that supplemental silicon may stimulate endothelial production of heparan sulfate proteoglycans that inhibit intimal hyperplasia.

Topics: Animals; Arteriosclerosis; Cardiovascular Diseases; Cholesterol, Dietary; Diet, Atherogenic; Endothelium, Vascular; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Models, Cardiovascular; Proteoglycans; Rabbits; Risk Factors; Silicon

In the present study we investigated the influence of elevated low density lipoprotein (LDL) concentration on endothelial permeability. Endothelial cells were cultured on microporous membranes until confluence and albumin, dextran and LDL transfer across endothelial monolayers was determined to assess macromolecular permeability. Exposure of proliferating aortic endothelial cells to LDL levels of more than 1 mg/ml LDL-cholesterol induced a concentration-dependent exponential increase in the permeability of confluent endothelial monolayers. Acute addition of high LDL concentration did not alter macromolecular permeability. Once elevated permeability was induced, it persisted. It was not readily reversible after addition of normal LDL levels. Change in permeability was accompanied by a selective decrease in basement membrane associated heparan sulfate proteoglycan (HSPG) content. The apparent parallel between the loss in endothelial barrier function and HSPG decrease implicates a connection between the two events. Prolonged, but not acute, incubation with antiserum directed against the core-protein of HSPG also led to increased permeability, suggesting a causal role of HSPG for the proper function of endothelium. The fact that non-atherogenic LDL-cholesterol levels had no effect indicates that a 'threshold' concentration for LDL-cholesterol may exist, leading to nondenuding injury in the endothelial barrier as an early event in development of atherosclerosis.

Topics: Animals; Aorta; Arteriosclerosis; Cell Membrane Permeability; Cells, Cultured; Endothelium, Vascular; Fibronectins; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Lipoproteins, LDL; Microscopy, Fluorescence; Proteoglycans; Swine

This study was designed to clarify the effects of vitamin E on the alterations in proteoglycan distribution and vascular permeability, which were examined by immunohistochemical and ultrastructural techniques in the aortas of cholesterol-fed guinea pigs. The animals were divided into three groups: a control group, a cholesterol group, and a vitamin E group. Serum levels of cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, and thiobarbituric acid-reactive substances were measured. An increase in thiobarbituric acid-reactive substances was observed in the cholesterol group compared with control and vitamin E groups. Intimal atheromatous lesions of the aorta were significantly decreased in the vitamin E group compared with the cholesterol group. Histochemically, an increased distribution of proteoglycans such as chondroitin, dermatan, and heparan sulfates and ruthenium red reaction products in the intima; decreased glycocalyx on the endothelial surface; and increased permeability to horseradish peroxidase were revealed in the cholesterol group compared with the vitamin E group. Hypercholesterolemia, resulting in superoxide production, may have contributed to the endothelial damage and increased permeability to plasma proteins and lipids in the vascular wall of the cholesterol group. However, vitamin E administration inhibited lipid deposition and development of this abnormal permeability associated with an irregular distribution of proteoglycan. These results suggest that vitamin E preserves the morphological and functional integrity of the vascular wall and may contribute to the inhibition of atherogenesis in cholesterol-fed guinea pigs.

Topics: Animals; Aorta; Arteriosclerosis; Capillary Permeability; Cholesterol; Cholesterol, Dietary; Chondroitin Sulfates; Dermatan Sulfate; Guinea Pigs; Heparitin Sulfate; Immunohistochemistry; Lipoproteins; Microscopy, Electron; Thiobarbituric Acid Reactive Substances; Vitamin E

We evaluated the effects of heparan-sulphate administration on clotting times, thromboelastographic parameters and serum thromboxane B2 levels in hypercholesterolemic rabbits with aortic atherosclerotic lesions (sudanophilic areas). 24 New Zealand male rabbits were divided into three groups of 8 animals each. Group A and B were fed a rabbit chow diet containing 0.7% of cholesterol whereas Group C was fed a standard rabbit diet without cholesterol. Group A was treated by subcutaneous route with 6 mg/kg/day of heparan sulphate. At the beginning of the study and after 3 and 6 months of treatment, serum cholesterol and thromboxane B2 levels were tested. Furthermore, at the end of the experiment, we evaluated plasma fibrinogen, aPTT, PT and TT values. The administration of heparan-sulphate in cholesterol fed rabbits produced: a reduction of plasma fibrinogen levels, without modifying aPTT and TT; a protective effect vs the lengthening in PT values, likely induced by cholesterol rich diet; a reduction of plasma thrombophilic activities and of aortic atheromasic involvement induced by dietetic cholesterol intake. However, increased serum thromboxane B2 levels, likely through a proaggregant activity were observed. We suggest that heparan-sulphate administration, in cholesterol fed rabbits, has a favourable effect on clotting parameters, while contrasting effects were found on platelet activity.

Topics: Animals; Arteriosclerosis; Blood Coagulation; Cholesterol, Dietary; Drug Evaluation, Preclinical; Heparitin Sulfate; Hypercholesterolemia; Male; Rabbits; Thromboxane B2; Time Factors

Proteoglycan production was examined in cultures of thioglycollate-elicited peritoneal macrophages obtained from White Carneau and Show Racer pigeons. Following a 24-h incubation in the presence of [35S]sulfate and [3H]serine, total production and distribution of 35S-labeled proteoglycan into media (60-65%), pericellular (21-27%), and intracellular (13-14%) compartments was similar in White Carneau and Show Racer macrophage cultures. Media proteoglycans consisted of high-molecular-weight chondroitin sulfate proteoglycan, low-molecular-weight chondroitin sulfate proteoglycan, and heparan sulfate proteoglycan. High-molecular-weight chondroitin sulfate proteoglycan was predominantly 6-sulfated (80%) and contained a core protein larger than 200 kd, whereas low-molecular-weight chondroitin sulfate proteoglycan was 4-sulfated and contained a 28-kd core protein. Pericellular proteoglycan was similar in size to low-molecular-weight proteoglycan and consisted of a predominantly 6-sulfated (75%) chondroitin sulfate proteoglycan and heparan sulfate proteoglycan. Intracellular 35S-labeled chondroitin sulfate and heparan sulfate were smaller than media and pericellular proteoglycans, suggestive of intracellular degradative processing.

Topics: Animals; Arteriosclerosis; Cells, Cultured; Chondroitin Sulfate Proteoglycans; Columbidae; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Macrophages; Molecular Weight; Peritoneal Cavity; Proteoglycans

The contents of three species of proteoglycans (PGs), heparan sulfate PG(HSPG), chondroitin sulfate PG(CSPG) and dermatan sulfate chondroitin sulfate PG(DSCSPG), in human thoracic aortas of subjects from districts of high (Beijin, in North China) and low (Nanning, in South China) prevalence of atherosclerosis in China were quantitated. Higher aortic HSPG and DSCSPG (but lower DS) in samples from Nanning than those from Beijing might be implicated in the lower prevalence of atherosclerosis in the former.

Topics: Adolescent; Adult; Aorta, Thoracic; Arteriosclerosis; China; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Chromatography, Gel; Chromatography, Ion Exchange; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Female; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Male; Prevalence; Proteoglycans

Topics: Animals; Arteriosclerosis; Cattle; Extracellular Matrix; Heparitin Sulfate; Macrophages; Muscle, Smooth, Vascular; Phenotype

We compared the effects of mild hypercholesterolemia and repeated endotoxin infusions on the biochemical composition of aortic intima and inner media of 24 piglets divided into 4 groups 5 days after weaning: controls on normal diet (group I); normal diet and endotoxin (group II); fat-supplemented diet (group III); and fat-supplemented diet and endotoxin (group IV). It was found that mild hypercholesterolemia increased the concentration of arterial esterified cholesterol and the relative amount of the fraction containing chondroitin sulphates A and C in total glycosaminoglycans. Endotoxin infusions partly prevented the increase of serum cholesterol caused by the fat-supplemented diet but had no independent effect on the arterial biochemical composition; nor did they affect the biochemical changes caused by hypercholesterolemia. When the results of all groups were combined, chondroitin sulphates A and C showed a significant positive correlation with the concentration of arterial esterified cholesterol and the percentage of linoleic acid in arterial cholesteryl esters. Serum total cholesterol did not correlate with arterial cholesterol fractions, but the ratio of high density lipoprotein-cholesterol to total serum cholesterol showed a negative association with arterial esterified cholesterol. The present findings indicate that (1) mild hypercholesterolemia is atherogenic in young piglets, and (2) changes in arterial glycosaminoglycan composition might be one of the earliest biochemical alterations in atherogenesis.

Topics: Animals; Aorta, Thoracic; Arteriosclerosis; Cholesterol; Chondroitin Sulfates; Dermatan Sulfate; Diet, Atherogenic; Endotoxins; Glycosaminoglycans; Heparitin Sulfate; Hyaluronic Acid; Hypercholesterolemia; Lipids; Muscle, Smooth, Vascular; Phospholipids; Reference Values; Swine

Diabetes mellitus and asthma have many antipodal features. Although both are common disorders, concurrence occurs less often than would be predicted. When co-existence does occur, the cases are generally mild, and effective treatment of one disease frequently exacerbates the other. The hypothesis is advanced that basilar membrane concentrations of heparan sulfate differ in these two diseases and that this difference may account for the antithetical features. An experimental basis for postulating increased concentrations of extracellular heparan sulfate in asthma and diminished concentrations in diabetes is cited. A rationale for tying these differences to the polar activities of cholinergic transmission and atherogenesis in the two diseases is advanced. Diminished heparan sulfate concentrations in diabetes may down-regulate the transmission of vagal impulses to insulin-producing pancreatic cells, and thereby impair both the continued vitality of these cells, and the acetylcholine modulated potentiation of glucose-induced insulin release.

Topics: Arteriosclerosis; Asthma; Diabetes Complications; Diabetes Mellitus; Heparin; Heparitin Sulfate; Humans; Models, Biological; Synaptic Transmission

Electrophoretic mobilities of heparitin sulfates (HS) from the thoracic aorta and the celiac bifurcation of atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons at four ages were examined. Atherosclerosis-susceptible White Carneau aortas contain, in addition to their normal HS component, a variant type of HS (HS') in pre, early- and moderately-atherosclerotic celiac foci which is not found in the thoracic regions of either breed or in Show Racer celiac foci at any age. These findings are interpreted to suggest a role of HS' in the pathogenesis of atherosclerosis and to propose an explanation for atherosclerotic susceptibility and resistance in pigeons.

Topics: Age Factors; Animals; Aorta; Arteriosclerosis; Columbidae; Electrophoresis, Cellulose Acetate; Glycosaminoglycans; Heparitin Sulfate; Species Specificity

Topics: Aging; Animals; Aorta, Thoracic; Arteriosclerosis; Chondroitin Sulfates; Columbidae; Dermatan Sulfate; Glycosaminoglycans; Heparitin Sulfate; Hyaluronic Acid; Species Specificity

Fifteen chicken tissues were examined for mast cells. Numerous mast cells were found in peritoneum and spleen. The sulfated mucopolysaccharides extracted from these two tissues, corresponding in amount to that in mast cells, were found to be dermatan sulfate, chondroitin sulfate and heparitin sulfate but no evidence of heparin. We have shown a similar situation occurs in the rabbit which is also highly susceptible to the production of atherosclerosis by diet. These observations provide further evidence of a role for heparin and mast cells in limiting atherogenesis.

Topics: Animals; Arteriosclerosis; Cell Count; Chickens; Chondroitin Sulfates; Dermatan Sulfate; Dogs; Female; Heparin; Heparitin Sulfate; Male; Mast Cells; Peritoneum; Rats; Spleen

Topics: Animals; Aorta; Arteriosclerosis; Cholesterol; Chondroitin; Dietary Fats; Female; Glycosaminoglycans; Heparitin Sulfate; Hexosamines; Hyaluronic Acid; Phospholipids; Rabbits; Thiouracil; Thyroxine

Topics: Animals; Aorta; Arteriosclerosis; Cholesterol; Chondroitin; Diet, Atherogenic; Female; Glycosaminoglycans; Heparitin Sulfate; Histocytochemistry; Hyaluronic Acid; Hypercholesterolemia; Rabbits