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)

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

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

One hypothesis for atherosclerotic lesion formation is the response to injury hypothesis. If catabolism of the ground substance of the intima of blood vessels is viewed as an injury, then inhibition of this catabolism could lead to a decrease in atherosclerotic lesions. Arylsulfatase B catalyses the desulfation of glycosaminoglycans in the catabolism of the intimal ground substance. We have found that ascorbic acid inhibits arylsulfatase B (Km = 2.06 mM, KI = 4.89 mM), thus providing a possible mechanism by which ascorbic acid may decrease atherosclerosis.
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PMID:Inhibition of arylsulfatase B by ascorbic acid. 178 40

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

Cardiac rupture occurs in 10 per cent of patients who die with acute myocardial infarction, but the pathogenesis remains unclear. Twenty randomly selected patients with cardiac rupture were reviewed retrospectively at autopsy, and the findings were compared with those of 20 age- and sex-matched control subjects who had died of acute transmural myocardial infarction without rupture. The times from the onset of chest pain to death were similar in the two groups (5.7 +/- 5.8 days for patients with rupture versus 4.2 +/- 4.9 days for control subjects), and there were no differences in the incidences of systemic hypertension, diabetes mellitus, hypercholesterolemia, history of myocardial infarction, or angina pectoris. The severity of coronary atherosclerosis was different in the two groups, with 55 per cent of the patients with cardiac rupture having single-vessel disease and 70 per cent of the patients without cardiac rupture having disease in three vessels. Additionally, the incidence of thrombosis was greater in patients with cardiac rupture than in those without. The inflammatory cell response in each patient was quantitated microscopically (number and type of leukocytes) in ten high-power fields. The inflammatory response was greater in patients with cardiac rupture. The number of eosinophils in the inflammatory response was significantly (P less than 0.01) greater in hearts associated with cardiac rupture (29.5 +/- 4 per cent) than in control hearts (11.7 +/- 3.1 per cent). It is postulated that eosinophils rich in arylsulfatase B, peroxidase, glucuronidase, beta-glycerophosphatase, major basic protein, and eosinophilic cationic protein may further weaken the necrotic myocardium and, in part, determine whether acute myocardial infarction will eventually result in cardiac rupture.
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PMID:Association of eosinophils with cardiac rupture. 399 34

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

Lipoprotein lipase (LPL) is rapidly and efficiently cleared from the circulation by the liver through an as yet unclear mechanism. In the present study, we determined the nature of LPL interactions with the liver parenchimal cell line HepG2 as compared to other cells in culture. Binding, cell association and degradation of 125I-labelled bovine milk LPL by HepG2 cells, normal and low density lipoprotein (LDL) receptor-negative human fibroblasts and Chinese hamster ovary (CHO) cells show similar values irrespective of source and origin. LPL metabolism in HepG2 cells was characterized by a high capacity to degrade the enzyme, an extremely high sensitivity to heparin and was inhibited by 60%-70% after treatment of the cells with sodium chlorate and heparinase (but not chondroitinase). These findings suggested an important role for heparan sulfate in the process of cell interaction and metabolism of LPL. To further clarify the role of heparan sulfate in determining the LPL-cell interactions, we compared the metabolism of LPL in wild type and mutant heparan sulfate-deficient CHO cells. Heparan sulfate-deficient CHO cells show a low capacity to bind and degrade LPL, about 10%-20% that of the wild type cells. In another set of experiments, we sought to determine whether LPL interactions with HepG2 cells are affected by triglyceride-rich lipoproteins. The results clearly show that whereas unlabeled LPL dramatically enhanced the metabolism of radioiodinated very low density lipoprotein (VLDL), unlabeled VLDL had no effect on radioiodinated LPL metabolism in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1995 Apr 07
PMID:Binding to heparan sulfate is a major event during catabolism of lipoprotein lipase by HepG2 and other cell cultures. 760 68


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