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

Cholesterol ester hydrolase activity was determined in preparations of rabbit and guinea pig aorta utilizing micellar and glycerol-dispersed cholesterol oleate substrates. Both substrate preparations demonstrated an acid pH optimum of 4--5 for the soluble and particulate rabbit media cholesterol ester hydrolase, suggesting a lysosomal origin for this activity. Approximately one-fifth of the total recovered activity was particulate. Particulate media preparations from guinea pig aorta also demonstrated cholesterol ester hydrolase activity at acid pH values with a definite optimum at pH 5 for the glycerol-dispersed substrate. However, in contrast to the rabbit media enzyme, activity was also observed at neutral pH with another optimum at pH 7. The supernatant enzyme from guinea pig media exhibited only a single pH optimum of 7. Cholesterol ester hydrolase activity from either rabbit or guinea pig media was not influenced by preincubation with cyclic AMP, ATP and protein kinase. The addition of chloroquine resulted in the inhibition of both the rabbit and guinea pig enzyme. Cholesterol ester hydrolase activity from rabbit and guinea pig media was also inhibited by phenyl methane sulfonyl fluoride; activity measured at pH 7 (guinea pig) was more sensitive to inhibition than activity measured at pH 5 (guinea pig and rabbit).
Atherosclerosis 1978 Sep
PMID:Characterization of cholesterol ester hydrolase activities in rabbit and guinea pig aortas. 3 Apr 61

Mice on an atherogenic diet for 40 days show a decrease in brain content of catecholamines, cyclic AMP and in dopamine degradation, and modification of the glycolytic pathway. The metabolic changes are paralleled by changes in behaviour, i.e. decrease in spontaneous motor activity and in conditioning avoidance response. The decrease in dopamine degradation and in behaviour parameters is partly due to the propylthiouracil present in the diet. Endovenous treatment with sonicated dispersions of bovine brain phospholipids induces a modification in the parameters of behaviour and metabolism. The possibility is discussed that some of the defects arising during the atherogenic diet are related with the establishment of a hypoxic state.
Atherosclerosis 1977 Jan
PMID:Effect of phospholipids on cholesterol-induced modifications in mouse brain. 18 79

Hypercholesterolemia caused a decrease in the activity of adenylcyclase in rabbit liver tissue and in thrombocytes; hypertriglyceridemia, which developed after administration of hydrocortisone, led to an increase in the activity of adenylcyclase and in the content of 3,5-AMP in adipose tissue. Activities of adenylcyclase, phosphodiesterase and content of prostaglandines E1 and F2alpha were measured in thrombocytes of 39 healthy men without any symptoms of of ischemic heart impairment, in 52 patients with coronary atherosclerosis of the III degree (by Myasnikov's classification) as well as in 12 patients during the period of rehabilitation after myocardial infarction. The activity of adenylate cyclase system was impaired in atherosclerosis. This phenomenon might be caused by alteration in concentration of glucocorticoids in the organism.
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PMID:[Cyclic adenosine monophosphate and atherogenic factors]. 20 91

The hyperreactive arterial endothelial cells have been introduced in this paper. They are characterized by their ability to transport particles too large for the small holes of the internal elastic lamina locating underneath the endothelial cells, such as carbon particles with the similar size of LDL, floating beta-lipoprotein, Lp(a) and especially of VLDL, into the subendothelial space from the blood stream by their abnormally strong contracting and phagocytosis-like activity. Large particles such as carbon particles with a size of 200 to 700 angstrom are too large to penetrate further through holes of the internal elastic lamina from the subendothelial space to muscular layers of the arterial wall, resulting in stagnating for a long time in the subendothelial space, thus showing the atherogenic property of the hyperreactive arterial endothelial cells. Such endothelial cells appear spotty and streaky in the localized endothelial lining of predominantly susceptible parts to atherosclerosis in susceptible animal species such as rabbit, chicken, and rhesus monkey especially densely in their atheromatous lesions, but do not generally appear in non-susceptible animals to atherosclerosis like rate and dog. They are extremely few in infant rabbit, but increase by age.They appear in hypertensive rat, showing a characteristic distribution even in small groups of arteriessuch as the circle of Willis. Cyclic AMP, and especially dibutyryl cyclic AMP, exhibited an inhibitory effect on the hyperreactivity of those cells. Cyclic AMP phosphodiesterase inhibitors, EG467 and eg626, exhibited a powerful inhibitory effect on the contracting and phagocytosis-like activity of those cells, as in the case of pyridinolcarbamate, which enhances enzymes to produce ATP and inhibits slightly cyclic AMP phosphodiesterase, although its inhibitory effect on cyclic AMP phosphodiesterase is weaker than that of EF467 and EG626. The usefulness of the inhibitors on cyclic AMP phospodiesterase of arterial endothelial cells and platelets and on that of brain, such as EG467 AND EG626, has been suggested in the treatment of atherosclerotic disorders, especially of cerebral atherosclerosis. Some of the hitherto desperate mental disability of the aged seem to be a promising target for treatment with cyclic AMP phosphodiesterase inhibitors.
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PMID:Hyperreactive arterial endothelial cells in atherogenesis and cyclic AMP phosphodiesterase inhibitor in prevention and treatment of atherosclerotic disorders. 23 47

Cilostazol, a cyclic AMP phosphodiesterase inhibitor, has been used as an antiplatelet agent. In the present study, we investigated the in vitro effect of cilostazol on DNA synthesis in rat aortic arterial smooth muscle cells (SMCs) in culture stimulated with fetal calf serum (FCS), platelet-derived growth factor (PDGF), insulin, or insulin-like growth factor-I (IGF-I). Micromolar concentrations of cilostazol inhibited [3H]thymidine incorporation into DNA and cell growth as determined by cell number and protein concentration. Treatment with cilostazol increased the intracellular concentration of cyclic AMP, suggesting that the inhibition of SMC proliferation by cilostazol may be mediated through increased levels of cyclic AMP. The results suggested that cilostazol, by interfering with the proliferation of arterial SMCs, may have potential to prevent initiation and progression of atherosclerosis.
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PMID:Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture. 128 92

Atherogenesis is associated with alterations in the properties of different cell types, including monocytes/macrophages (foam cell formation), platelets (increased aggregation), endothelial cells (injury), and smooth muscle cells (SMCs) (lipid accumulation or foam cell formation). Oxidized low density lipoproteins (ox-LDL) play a key role in this vascular pathology. This study investigated the ability of ox-LDL to elicit chemical signaling events in cultured human vascular smooth muscle cells (VSMCs). Ox-LDL was found to stimulate phospholipase C-mediated phosphoinositide turnover in human VSMCs. This response occurred rapidly (within 1 minute) and at low concentrations of ox-LDL (half-maximal effective concentration, approximately 5 micrograms/ml). Ox-LDL-stimulated inositol phosphate accumulation in human VSMCs was inhibited by pretreatment of cells with phorbol 12-myristate 13-acetate and with compounds that elevate cyclic AMP or cyclic GMP. Ca2+ antagonists also blocked the effects of ox-LDL on phosphoinositide turnover. Inhibitors of receptor-endocytotic processes (including receptor clustering, cross-linking, and cytoskeleton-dependent internalization) effectively prevented ox-LDL-induced inositol phosphate generation. The data suggest that ox-LDL promotes phospholipase C-mediated phosphoinositide turnover in a manner analogous to that for other Ca(2+)-mobilizing hormones. The results also support an association between phosphoinositide turnover and receptor-mediated endocytosis. Prevention of the direct effects of ox-LDL on SMCs could prove an interesting therapeutic avenue for the prevention of atherosclerosis.
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PMID:Oxidized low density lipoproteins stimulate phosphoinositide turnover in cultured vascular smooth muscle cells. 131 38

Hypercholesterolemia and hypertension are two of the major risk factors associated with increased atherosclerotic vascular disease. An abnormal platelet function is one of the mechanisms proposed to participate in atherogenesis. This study was undertaken to find out whether hypercholesterolemia in hypertensive patients can change platelet lipid composition and reactivity. Twenty-nine untreated hypertensive patients were distributed into 3 age, body mass index and blood pressure-matched groups according to their plasma cholesterol levels (normal, borderline or elevated, group NC, BC and HC respectively). Their platelet lipid composition, cytosolic Ca2+ concentration, cyclic AMP content and aggregating response to ADP and collagen were determined. Platelet from group HC patients were characterized by reduced cyclic AMP content (evaluated in the presence and absence of a platelet phosphodiesterase inhibitor) and aggregating responses to ADP and collagen, increased palmitic acid content and decreased arachidonic, eicosapentaenoic and docosatetraenoic and pentaenoic acid content, resulting in a lowered polyunsaturated to saturated fatty acid ratio (P less than 0.001). In contrast, platelet cytosolic Ca2+ concentration, DPH steady-state anisotropy and cholesterol to phospholipid molar ratio were not significantly changed. This indicates that hypercholesterolemia is accompanied in hypertensive patients by marked changes in platelet fatty acid composition, cyclic AMP content and response to aggregating agents. These changes, which clearly differ from those induced by in vitro cholesterol loading, could reflect not only the balance between LDL and HDL stimulation but also an adaptation to hemodynamic perturbations.
Atherosclerosis 1992 Jun
PMID:Biochemical and functional alterations associated with hypercholesterolemia in platelets from hypertensive patients. 132 32

It has been generally accepted that platelets play etiological roles for the development of atherosclerosis and arterial thrombosis. Platelet activation may be dependent upon the cytosolic free Ca2+ concentration ([Ca2+]i), and regulated by PGI2 and endothelium-derived relaxing factor (EDRF) released by vascular endothelium. We have studied here the effect of endothelial cells (EC) on platelet activation and intracellular Ca2+ mobilization. Effluent of non-stimulated EC column inhibited thrombin-induced platelet aggregation and intracellular Ca2+ mobilization. An addition of this effluent to platelet suspension leaded to increase in intraplatelet cyclic AMP (cAMP) which was inhibited by the treatment of indomethacin to EC, suggesting that this effect was involved in PGI2 released by EC. On the other hand, effluent of thimerosal-stimulated EC column inhibited platelet aggregation and increase in [Ca2+]i stimulated with thrombin, and leaded to increase in intraplatelet cyclic GMP (cGMP). But the treatment of indomethacin to EC had no effect of this inhibition. The effect of thimerosal-stimulated EC was inhibited by the addition of 1-NG-monomethylarginine (NMA), EDRF/NO inhibitor, suggesting that EDRF released by thimerosal-stimulated EC produced an increase in cGMP and inhibited platelet activation. Although forskolin-induced in cAMP caused a marked prevention of inositol 1, 4, 5-trisphosphate (IP3) production stimulated with thrombin, 8-bromo cGMP and EDRF-induced increase in cGMP had no effect of IP3 production. An increase in cAMP and cGMP was considered to inhibit intracellular Ca2+ mobilization by different mechanisms in platelets.
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PMID:[Intracellular Ca2+ mobilization and its regulation in platelet activation]. 165 28

Foam cell formation via lipid accumulation through the scavenger receptor in human monocyte/macrophages is believed to be one of the earliest events in atherogenesis. In this study we demonstrate that stimulation of the scavenger receptor activates monocytes to produce interleukin-1 (IL-1). Polyinosinic acid (poly I) and fucoidan, both ligands known to bind to the scavenger receptor, induced IL-1 beta production in human monocytes. Polycytidylic acid, a structurally related compound to poly I, which does not bind to the scavenger receptor, was used as a negative control and had virtually no effect on IL-1 production. THP-1 cells, which normally do not express scavenger receptors, were almost unresponsive to poly I and fucoidan. PMA priming, which has been reported to up-regulate scavenger receptor expression in THP-1 cells, significantly enhanced IL-1 production by fucoidan and poly I. IL-1 produced by scavenger receptor stimulation was shown to be secreted extracellularly, and biologically active. Scavenger receptor-mediated IL-1 production was inhibited by H7, a protein kinase C inhibitor, and enhanced by IBMX, an inhibitor of cyclic AMP degradation, suggesting a synergistic effect of protein kinase C and cyclic AMP-mediated signal transduction pathways in scavenger receptor-mediated IL-1 production. Due to the potentially deleterious effects of IL-1 on the vessel wall, IL-1 produced by ligand binding to the scavenger receptor in human monocytes may play a role in the pathogenesis of atherosclerosis.
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PMID:Induction of interleukin-1 production by ligands binding to the scavenger receptor in human monocytes and the THP-1 cell line. 166 75

Cytokines such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and gamma-interferon (IF) are produced by activated hematopoietic cells. They possess antiviral activity and have other biological activities such as induction of cell proliferation and hemorrhagic necrosis of tumors. Since herpes simplex virus (HSV) infection of human vascular cells is known to produce a biochemical and cytopathological effect virtually indistinguishable from atherosclerosis, we hypothesized that these cytokines many prevent cholesteryl ester (CE) accumulation in arterial smooth muscle cells (SMC) that is seen with herpesvirus infection. We now report that TNF and IL-1 but not gamma-IF prevent CE accumulation in HSV-infected arterial SMC by induction of cyclic AMP-dependent CE hydrolysis. This effect is mediated through the arachidonate 12-lipoxygenase pathway via 12-HETE since pretreatment of cells with several lipoxygenase inhibitors abolishes the antiviral effect and 12-HETE is the major (greater than 99%) lipoxygenase metabolite produced by these cells. This conclusion is further based on our observations that TNF and IL-1 enhance 12-HETE production in SMC and that 12-HETE significantly increases both intracellular cyclic AMP and lysosomal CE hydrolysis. Moreover, dibutyryl cyclic AMP restored a normal phenotype in these virally infected cells. Collectively, these findings identify for the first time a biochemical mechanism involved in the reduction of lipid accumulation in virally infected arterial SMC by these potent cytokines.
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PMID:Evidence for cytokine regulation of cholesterol metabolism in herpesvirus-infected arterial cells by the lipoxygenase pathway. 210 32


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