Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

The changes in levels of glycosaminoglycans (GAGs) of the intima and media of the human artery in atherosclerosis were determined by a recently introduced two-dimensional electrophoresis technique that permits direct measurments of each of these macromolecules. To identify the arterial GAGs, they were fractionated by chromatography on a DEAE-Sephadex A-25 column, and the resulting three fractions (hyaluronic acid [HA], heparan sulfate [HS], and the partially separated chondroitin sulfates B [CSB] and C [CSC]) were analyzed for their electrophoretic mobilities by this electrophoretic method, for their digestability by highly specific hydrolases (leech hyaluronidase, heparinase, and chondroitinases ABC and AC) and for their iduronic acid content. From these studies we concluded that normal and atherosclerotic human aortas contain CSB, CSC, HA, and HS. Further, we demonstrated that CSB is a hybrid consisting of approximately 40% CSA and 60% CSB and that CSC appears to be a polymer consisting essentially of glucuronic acid and N-acetylgalactosamine-6-sulfate. Classical CSA as well as chondroitin (CH) were not present in detectable amounts. In the relatively normal intima, the mean concentrations of the GAGs were found to be 4.7, 20.9, 1.3, and 5.1 mg/g of dry, defatted, decalcified tissue for CSB, CSC, HA, and HS, respectively. With the progression of atherosclerosis, there was a pronounced decrease in the total GAG content (from 32 to 18 mg) associated with a decrease in the CSC and HS levels but without a change in the HA concentrations. Of particular interest, however, was the increase in the CSB level. In the media whose total GAG content averaged approximately 20 mg, no significant changes in these GAG levels were noted with the progression of the disease except for that of CSC. These findings may be important in explaining the increased lipoprotein and collagen deposition in the diseased aorta.
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PMID:The glycosaminoglycans of the human artery and their changes in atherosclerosis. 13 44

A large amount of plasma low density lipoprotein is present in human aortic intima, and this can be removed and measured by electrophoresis directly from the minced tissue into an antibody-containing gel. We now find that, in addition to this electrophoretically mobile lipoprotein, there is an immobilized lipoprotein fraction than can be released from lesions by incubation of the tissue sample with plasmin or other proteolytic enzymes after the mobile lipoprotein has been removed. The concentration of immobilized lipoprotein is highly correlated with the concentration of the residual cholesterol (not mobile on electrophoresis) that has accumulated in the tissue (r = 0.702; P less than 0.001). Thus, in normal intima and early gelatinous lesions it is about 15% of the concentration of mobile lipoprotein, whereas in the atheroma lipid layers of fibrous or gelatinous plaques it may be 2 or 3 times greater than the concentration of mobile lipoprotein. This suggests that immobilization of plasma lipoprotein is an intermediate step in the irreversible deposition of extracellular cholesterol in atherosclerotic lesions. Incubation with plasmin allowed maximum release of lipoprotein: plasmin = crude collagenase greater than trypsin greater than "pure" collagenase greater than chondroitinase ABC in order of their relative effectiveness. The concentration of immobilized lipoprotein was significantly correlated (r = 0.793; P less than 0.001) with the concentration in the tissue of fibrin or other insoluble derivatives of fibrinogen ("fibrin"). In aliquots of lesions incubated with varying amounts of plasmin for varying times there was a constant relation between release of lipoprotein and release of fibrin-degradation products. Together, these findings suggest that the lipoprotein is associated with insoluble "fibrin". This appears to be of considerable clinical interest, suggesting a synergism between lipoprotein and fibrinogen in the accumulation of lipid in lesions.
Atherosclerosis 1976 Oct
PMID:The release of an immobilized lipoprotein fraction from atherosclerotic lesions by incubation with plasmin. 18 79

Heparin-like glycosaminoglycans (GAG) were isolated from commerical Vessel and their biologic properties studied. Vessel was found to be a mixture of chondroitin sulfates, dermatan sulfate and heparin-like GAG. Chondroitin sulfates and dermatan sulfate in Vessel were hydrolyzed by chondroitinase ABC and the residual Vessel was fractionated on a Dowex-1 Cl- column eluting with a stepwise-increasing concentration of NaCl (1.2--4.0 M). The major fractions eluted at 1.6 M and 1.8 M NaCl were tentatively identified by chemical analysis as heparin-like GAG with somewhat lower sulfate content than standard heparin. Both fractions had lipoprotein lipase-releasing activity and anticoagulant activity similar to heparin, but 1.6 M NaCl fraction had a third of the anticoagulant activity of standard heparin. The 1.8 M NaCl fraction complexed with serum lipoproteins similarly to heparin. In preliminary studies cholesterol-fed rabbits treated with Vessel exhibited somewhat less atherosclerosis than controls.
Atherosclerosis 1978 Oct
PMID:Studies of glycosaminoglycan composition and biologic activity of Vessel, a hypolipidemic agent. 72 39

The presence of herpes simplex virus (HSV) and cytomegalovirus (CMV) nucleic acid and/or antigen was demonstrated in the coronary arteries and thoracic aortas of young trauma victims by the in situ DNA hybridization and ABC immunoperoxidase methods, respectively. Epstein-Barr virus (EBV) nucleic acid and capsid antigen were not detected in the arteries sampled in this study. Of 8 subjects in which virus was detected in the coronary arteries, 6 were positive for HSV and 2 for CMV; of 7 cases positive in the thoracic aorta, 5 were identified as HSV and 2 as CMV. Viral DNA and/or antigen were found in occasional cells in the intact luminal surface and in focal clusters of spindle-shaped or "foamy" cells in the intimal layer. The histologic findings indicate that HSV and CMV are associated with areas showing early or advanced atheromatous changes in the coronary arteries and with lesion-free as well as lesion areas in the thoracic aorta. The virologic findings support the concept that herpes-viruses may potentially play a direct or indirect role in the pathogenesis of human atherosclerosis.
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PMID:Herpesviridae in the coronary arteries and aorta of young trauma victims. 282 95

The adhesion of immunoglobulins (IgG) and beta-migrating very low density lipoproteins (beta-VLDL) to aortic valve cusps from normolipidemic and hypercholesterolemic rabbits is associated with cytochemical changes in the endothelial glycocalyx. Endothelial surface changes are characterized by (1) enzymatic degradations with neuraminidase (NEU), chondroitinase ABC (CABC) or AC, and heparitinase (HPT); and (2) affinity cytochemistry with avidin-ferritin, protein A-HRP, and beta-VLDL-colloidal gold. NEU facilitated IgG deposition on cells from normolipid animals; however, tandem treatment with NEU and CABC increased beta-VLDL but prevented IgG interactions. The addition of HPT was required to eliminate beta-VLDL activity. The cells lining the arterial surfaces of cusps from hypercholesterolemic animals were reactive for endogenous IgG and beta-VLDL-gold. CABC enhanced the binding of the latter but removed most of the IgG. All reactivity was prevented by CABC and HPT. These findings suggest that the reduction of sialic acid residues and exposure of deeper lying glycosaminoglycans in the endothelial glycocalyx favor the interaction of blood-borne elements at natural sites of disturbed blood flow in dietary hypercholesterolemia.
Atherosclerosis 1987 Dec
PMID:Interactions of IgG and beta-VLDL with aortic valve endothelium from hypercholesterolemic rabbits. 332 1

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

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

The synthesis and secretion of sulfated glycosaminoglycans (GAGs) by aorta explant monolayers cultured from atherosclerosis-susceptible White Carneau (WC) and atherosclerosis resistant Show Racer SR pigeons have been compared. Primary cultures of WC pigeon aorta incorporation three to four times as much 35-S-sulfate into trichloroacetic acid (TCA) soluble, nondialyzable material that is over 90% sensitive to chondroitinase ABC digestion when compared with parallel cultures of SR pigeon aorta. Qualitatively, the GAGs produced by WC and SR aorta explants were similar in that their electrophoretic profiles were characterized by a prominent slow migrating band that did not coelectrophorese with known GAG standards, a discrete hyaluronic acid and heparan sulfate band and a broad band containing dermatan sulfate and chondroitin 4- and 6-sulfate. Enzyme digestion of the labeled material revealed that cultures of each breed synthesized and secreted predominantly chondroitin sulfate (approximately 60%) with moderate amounts of dermatan sulfate (approximately 35%) and little heparan sulfate (< 5%). This pattern of GAG distribution resembled that of GAGs present in pigeon aortas in vivo. Although differences in the relative percentages of each type of GAG produced by aorta explant cultures from each breed were not evident, densitometric tracings and radioisotopic activity of the electrophoretically separated GAGs indicate more sulfated GAG of each type present in WC as compared with SR cultures. Glycosaminoglycan-containing proteoglycans were also demonstrated morphologically in the aorta explant monolayers of each breed and resembled aortic proteoglycans in vivo. Proteoglycans in vitro existed as discrete 200-500-A polygonal granules, exhibited a marked affinity for ruthenium red, were intimately associated with each other through filamentous projections as well as with other components of the intercellular matrix (collagen and elastic fiber), and were completely sensitive to chondroitinase ABC digestion. This culture system is offered as a useful model for future investigations concerned with relating GAG metabolism to susceptibility to atherosclerosis.
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PMID:Differences in the synthesis and secretion of sulfated glycosaminoglycans by aorta explant monolayers cultured from atherosclerosis-susceptible and -resistant pigeons. 744 97

A chondroitin sulfate-dermatan sulfate proteoglycan was isolated from bovine aorta intima by extraction of the tissue with 4 M guanidine hydrochloride. The proteoglycan was purified by CsCl isopycnic centrifugation followed by gel filtration and ion exchange chromatography. A monoclonal antibody C8F4 was developed to this core protein. The characteristics and specificity of the antibody were studied by an enzyme-linked immunosorbent assay (ELISA) using an alkaline phosphatase conjugated antibody (goat anti-mouse IgG). The antibody binding to the core protein was found specific and optimal at pH 7.0. The antibody recognizes either intact chondroitin sulfate-dermatan sulfate proteoglycan monomer, chondroitinase ABC digested monomer or chemically deglycosylated proteoglycan. Free chondroitin sulfates, keratan sulfate and hyaluronic acid did not compete for the antigenic sites in ELISA. Limited hydrolysis of the core protein by trypsin resulted in three peptides and only the peptide with a molecular weight M(r) = 40,000 was found capable of binding to hyaluronic acid. The antibody C8F4 recognized this hyaluronic acid binding peptide but did not recognize the other two peptides suggesting that the epitope(s) for this antibody is in the hyaluronic acid-binding region of the core protein. The antibody recognized the core proteins from bovine nasal cartilage proteoglycan and human aorta proteoglycan but did not recognize bovine aorta link protein, bovine serum albumin, human serum albumin, human transferrin, collagen Type I and fibronectin. The antibody was found useful to localize proteoglycans in atherosclerotic lesions in human aorta by immunohistochemical techniques.
Atherosclerosis 1993 Jan 25
PMID:A monoclonal antibody that recognizes hyaluronic acid binding region of aorta proteoglycans. 768 Dec 90

Dermatan sulfate proteoglycans (DSPG) were extracted from intima-media of grossly normal aortic tissue of White Carneau pigeons and were purified by ion exchange chromatography on DEAE-Sephacel followed by size exclusion chromatography on Sepharose CL-4B. The major aortic DSPG had an average size of 310 kDa. The core protein resulting from treatment of the PG with chondroitinase ABC: (1) was found to be approximately 48 kDa by SDS-polyacrylamide gel electrophoresis; (2) was recognized by monoclonal antibody (Mab) 2-B-6 but not by Mab 3-B-3 on Western blots, indicating the presence of delta Di-4S and absence of delta Di-6S; (3) was glycosylated with Asn-linked oligosaccharides; (4) contained a high content of Asx, Glx and Leu, similar to that found for core proteins of this size from other tissues and species and (5) contained an N-terminal sequence (Asp-Glu-Gly-Xaa-Ala-Asp-Met-Pro-Pro-Xaa-Asp-Asp-Pro-Val- Ile-(ile)-Gly-Phe-), which was similar to sequences of DSPG core proteins previously described as 'decorin' and distinct from DSPG described as 'biglycan'. The results suggest that the major DSPG of aorta can be classified as a decorin molecule. The overall size of the DSPG in aorta was larger than decorin molecules described in non-arterial tissues of other species. Evidence is presented to conclude the larger size results from more than one dermatan sulfate-glycosaminoglycan chain.
Atherosclerosis 1993 Jan 04
PMID:Structural properties and partial protein sequence analysis of the major dermatan sulfate proteoglycan of pigeon aorta. 845 55


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