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)

A part of low density lipoproteins (LDL) isolated from the blood of healthy subjects and patients with coronary atherosclerosis bind to a Sepharose-linked Ricinus communis agglutinin, a lectin that interacts specifically with galactose residues. Bound LDL can be replaced by galactose, but not other saccharide constituents of the LDL molecule (mannose, glucose, N-acetylglucosamine, sialic acid). Bound LDL subfraction has a 2-3-fold lower content of sialic acid as compared with unbound LDL. The blood content of desialylated LDL in atherosclerotic patients was about 3-fold higher (1.5- to 6-fold) than in healthy subjects. Desialylated LDL induced a 2- to 4-fold more intensive accumulation of total cholesterol in cultured human aortic intimal cells. Unbound LDL had no effect on intracellular deposition of lipids. It is suggested that the subfraction of desialylated LDL may be responsible for the atherogenicity of LDL isolated from blood of atherosclerotic patients.
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PMID:Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography. 232 61

In order to assess the possible utility of lectin binding to identify the cellular components of fixed arterial lesions we studied lectin binding in experimental rabbit and monkey vessels, as well as in human atherosclerotic arteries obtained at surgery. The avidin-biotin-peroxidase technique was used to localize the binding of the following biotinylated lectins: Concanavalin A (Con A), Dolicho biflorus agglutinin (DBA), soybean agglutinin (SBA), peanut agglutinin (PNA), Phaseolus vulgaris agglutinin (PHA), Ricinus communis agglutinin (RCA), wheat germ agglutinin (WGA), and Ulex europaeus agglutinin (UEA). PHA demonstrated specific cytoplasmic staining of macrophages in rabbit, monkey, and human tissues and differentiated macrophages from other cell types in atherosclerotic lesions. When morphometric comparisons were made between lesion PHA staining and another macrophage marker, acid lipase, very similar results were obtained. Con A, RCA, and WGA stained macrophages intensely and differentiated them from other cell types in normal reticuloendothelial tissues and lesions, but also stained smooth muscle cells and endothelial cells when these cells developed lipid vacuoles. UEA stained the endothelium of vasa vasorum consistently in human arteries, but staining of artery lumen endothelium was variable. Endothelial cells of rabbit or monkey vessels did not stain with UEA. DBA, PNA, and SBA did not consistently stain any cellular structures in arteries. PHA was found to be an excellent marker to differentiate and quantify macrophages in glutaraldehyde or formalin-fixed, paraffin-embedded experimental and human atherosclerotic lesions. Con A, RCA and WGA merit further detailed study in conjunction with other histochemical tests as possible markers of functional changes in arterial cells during lesion development.
Atherosclerosis 1986 Sep
PMID:Lectin binding to distinguish cell types in fixed atherosclerotic arteries. 353 93

Endothelia lining the 2 surfaces (arterial and ventricular) of the posterior cusp of aortic valves from normocholesterolemic, New Zealand white rabbits were found to display pleomorphic surface features characterized by differences in cellular shape and orientation to the direction of blood flow, microappendage populations (microvilli and blebs), nuclear contours and the surface reactions of cationic dyes (RR, AB) and peroxidase-conjugated lectins (Con A, Limulin, WGA). With the aid of SEM and TEM, the cells lining the arterial surfaces appeared relatively smooth and flattened with a moderate to heavy reaction of the carbohydrate cell coat at the blood interface. By contrast, the contours of the endothelia lining the ventricular surfaces were noticeably raised with numerous plasmalemmal microappendages and only a moderate dye/lectin reaction. Observations of similar endothelial populations from diet-induced, hypercholesterolemic rabbits (500 mg/dl) revealed a variety of dramatic changes in the cells lining the arterial surfaces of the valvular cusps. No severe changes were observed in the endothelia of the ventricular surfaces. Such findings are suggestive further of the importance of the interaction between the environment and the endothelial cell coat as influencing factors in the onset of intramural lipid infiltration.
Atherosclerosis 1985 Mar
PMID:Surface responses of aortic valve endothelia from diet-induced, hypercholesterolemic rabbits. 399 84

We have described methodology for the isolation and quantitation of glycosaminoglycans present in human plasma. Plasma glycosaminoglycans can be quantitatively adsorbed on a DEAE-Sephacel ion exchanger and eluted with a salt gradient as two groups: a low-charge fraction and a high-charge fraction. The low-charge fraction consists of chondroitin sulfate with a low sulfate content and the high-charge fraction consists of heparan sulfate, chondroitin sulfate, and keratan sulfate (type I). We have determined the plasma concentration of each of these glycosaminoglycans in six normal human subjects. We have established that none of the glycosaminoglycans in plasma are covalently linked to plasma proteins. All are isolated as complexes with plasma proteins in noncovalent linkages. The glycosaminoglycans in the low-charge fraction are bound with high affinity to a single plasma glycoprotein by a lectin-type bond that can be disrupted by a simple glycoside. The high-charge fraction contains three major proteins and several minor proteins associated with the glycosaminoglycans by both lectin-type and ionic bonding. The plasma proteins associated with glycosaminoglycans represent less than 0.5% of the total plasma proteins. Little is known about the physiologic role of the plasma glycosaminoglycans as components of metabolic processes. Because glycosaminoglycans have been implicated in lipid metabolism and atherosclerosis, we tested all of these compounds, isolated in free form, on the in vitro hydrolysis of triglycerides by lipoprotein lipase. Plasma heparan sulfate stimulated the rate of this reaction severalfold. All other plasma glycosaminoglycans were inactive. Thus, plasma heparan sulfate may play an important role in plasma lipoprotein metabolism.
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PMID:Isolation and characterization of glycosaminoglycans in human plasma. 405 61

P-selectin is a transmembrane adhesion receptor specific to platelets and endothelial cells. It has an N-terminal lectin domain that recognizes specific carbohydrate moieties on monocytes, neutrophils and some other subsets of leukocytes. P-selectin is stored in granules and is expressed on the plasma membrane only after the cells are stimulated by vascular injury or during inflammation. Physiologically P-selectin is likely to be involved in the recruitment of leukocytes that promote wound healing and fight infection. There are many disorders in which the excessive recruitment of leukocytes is characteristic, including chronic inflammation, atherosclerosis, arthritis, diabetes, asthma and reperfusion injury. Because certain cancer cells also express the ligand for P-selectin it is possible that this receptor is involved in metastasis. To study the specific role of P-selectin in these pathological processes, we have prepared a mouse lacking P-selectin through gene targeting. Leukocyte interaction with the vessel wall is defective in these animals as leukocytes do not roll in the mesenteric venules and their extravasation at sites of inflammation and vessel injury is limited. We are testing these animals in models of the various diseases mentioned above in order to evaluate when the absence of P-selectin is beneficial.
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PMID:P-selectin knockout: a mouse model for various human diseases. 758 33

Modified low-density lipoprotein (LDL) with a low sialic acid content was found in the blood of patients with coronary atherosclerosis. This desialylated lipoprotein causes lipid accumulation in arterial smooth-muscle cells and stimulates cell proliferation and production of the extracellular matrix, i.e., induces all atherogenic manifestations at the cellular level. We have developed a lectin-sorbent assay for the determination of desialylated LDL in sera. The assay is based on the binding of desialylated LDL by immobilized Ricinus communis agglutinin with subsequent measurement of lipoprotein through use of anti-apolipoprotein (apo) B antibody. The assay is sensitive to desialylated apo B concentrations as low as 5 micrograms/L. The intraassay and interassay CVs were 4.8% and 11.3%, respectively. Comparison between the lectin-sorbent assay and a lectin chromatographic technique showed a good correlation. This determination of modified desialylated LDL in human serum with high accuracy and reproducibility may help establish the diagnostic value of this lipoprotein as a risk factor of atherosclerosis.
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PMID:Modified (desialylated) low-density lipoprotein measured in serum by lectin-sorbent assay. 760 Jun 81

Leukocytes play some important roles in pathophysiological conditions, such as inflammation, atherosclerosis, etc. It has been known that adhesion of leukocytes to vascular endothelial cells is the initial step in these conditions. Leukocytes adhere to endothelial cells utilizing adhesion molecules, such as CD11/CD18-I CAM-1, sialyl Lewis X-ELAM-1, etc. In this paper. The structure, expression and function of ICAM-1 and ELAM-1 on the endothelium is explained. ICAM-1 is a 90 kd inducible surface glycoprotein that belongs to the immunogloblinsuperfamily. Expression of ICAM-1 on the endothelium exposed to TNF, IL-1, LPS and IFN-gamma increase. This expression peaks at about 24 hours. ICAM-1 binds to CD11a/CD18 on the surface of leukocytes and takes part in the transendothelial migration. ELAM-1 is a 115 kd inducible glycoprotein, that consists of one lectin domain, one EGF-like domain and six complement regulatory like molecules. Endothelial cells will express ELAM-1 following stimulation by TNF, IL-1 and LPS. This expression peaks at 4-6 hours, declines at 24 hours. ELAM-1 binds to sialyl Lewis X on the leukocytes and participates in the rolling phenomenon, the first step of adherence to endothelium. Clarification of the mechanism of adhesion molecules expression may facilitate the treatment and prevention of vascular diseases.
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PMID:[Molecular biology of adhesion molecules--structure, expression and function of ICAM-1 and ELAM-1]. 768 87

Oxidatively modified lipoproteins have been implicated in atherogenesis, but the mechanisms that promote oxidation in vivo have not been identified. Myeloperoxidase, a heme protein secreted by activated macrophages, generates reactive intermediates that oxidize lipoproteins in vitro. To explore the potential role of myeloperoxidase in the development of atherosclerosis, we determined whether the enzyme was present in surgically excised human vascular tissue. In detergent extracts of atherosclerotic arteries subjected to Western blotting, a rabbit polyclonal antibody monospecific for myeloperoxidase detected a 56-kD protein, the predicted molecular mass of the heavy subunit. Both the immunoreactive protein and authentic myeloperoxidase bound to a lectin-affinity column; after elution with methyl mannoside their apparent molecular masses were indistinguishable by nondenaturing size-exclusion chromatography. Peroxidase activity in detergent extracts of atherosclerotic lesions likewise bound to a lectin column and eluted with methyl mannoside. Moreover, eluted peroxidase generated the cytotoxic oxidant hypochlorous acid (HOCl), indicating that enzymatically active myeloperoxidase was present in lesions. Patterns of immunostaining of arterial tissue with antihuman myeloperoxidase antibodies were similar to those produced by an antimacrophage antibody, and were especially prominent in the shoulder region of transitional lesions. Intense foci of myeloperoxidase immunostaining also appeared adjacent to cholesterol clefts in lipid-rich regions of advanced atherosclerotic lesions. These findings identify myeloperoxidase as a component of human vascular lesions. Because this heme protein can generate reactive species that damage lipids and proteins, myeloperoxidase may contribute to atherogenesis by catalyzing oxidative reactions in the vascular wall.
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PMID:Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions. 804 Feb 85

The effect of Lp(a) on lipid metabolism in cells cultured from unaffected human aortic intima has been investigated. Lp(a) isolated from the blood of healthy subjects failed to alter intracellular neutral lipid content. On the other hand, Lp(a) obtained from coronary atherosclerosis patients induced a 1.5- to 2-5-fold increase in intracellular levels of free and esterified cholesterol and triglycerides. The sialic acid content of patients' Lp(a) was 2.5-fold lower as compared with that of healthy subjects' Lp(a). Healthy donors' Lp(a) in vitro desialylated with neuraminidase were able to accumulate lipids within the cells. Using lectin-chromatography on Ricinus Communis agglutinin-agarose, Lp(a) was divided into subfractions differing by sialic acid content. Desialylated (sialic acid-poor) Lp(a), but not sialylated lipoproteins, were capable of increasing the intracellular content of total cholesterol. Desialylated but not sialylated Lp(a) formed aggregates during incubation under cell culture conditions. Isolated aggregates of desialylated Lp(a) induced lipid accumulation in cells. Elimination of Lp(a) aggregates from cultural medium prevented the increase of intracellular lipids. Complexes of Lp(a) with the matrix components and antibodies increased lipid level in cultured cells. We assume that formation of large particles of desialylated Lp(a) aggregates or Lp(a)-containing complexes is a necessary step for lipid accumulation in human intimal cells.
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PMID:Effect of lipoprotein(a) on lipid metabolism of cultured human intimal aortic cells. 818 10

In order to investigate processes, such as atherosclerosis and inflammation in vitro, it is necessary to obtain viable and pure endothelial cell cultures from human hearts. To this end, endothelial cells were isolated and cultured from the micro- and macrovasculature of human hearts obtained during heart transplantation. Isolation of capillaries after enzymatic digestion of heart muscle provided a source of microvascular endothelial cells. Contaminating non-endothelial cells were removed by a new technique: paramagnetic beads linked to the lectin ulex europaeus I (UEA-I) were used to select endothelial cells. The resulting cultures contained less than 2% of non-endothelial cells, as judged from immunological staining and fluorescence-activated cell sorting. Both types of endothelial cell displayed typical endothelial properties. They were all positive for factor VIII-related antigen and expressed the endothelial-specific adhesion molecules, CD31 and E-selectin (ELAM-1), after stimulation with cytokines. In addition, they could be labelled with Dil-Ac-LDL, contained angiotensin converting enzyme activity and secreted tissue plasminogen activator, thus demonstrating that typical endothelial functions were preserved in culture.
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PMID:Cultivation and characterization of micro- and macrovascular endothelial cells from the human heart. 829 83


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