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)

Prostacyclin is a product of arachidonic acid metabolism generated by the vessel wall of all mammalian species studied including man. Prostacyclin is a potent vasodilator and the most potent inhibitor of platelet aggregation so far described. It inhibits platelet aggregation through stimulation of adenylate cyclase leading to an increase in cyclic AMP in the platelets. The enzyme which synthesizes prostacyclin is mainly localized in the endothelial layer of the vascular wall. Prostacyclin can also be a circulating hormone constantly released by the pulmonary circulation. On the basis of these observations we proposed that platelet aggregability in vivo is controlled via a prostacyclin mechanism. In contrast to the vessel wall, in blood platelets arachidonic acid is converted by the enzyme thromboxane synthetase to a potent vasoconstrictor and proaggregating substance, thromboxane A2. Therefore arachidonic acid is metabolized in the vessel wall and the platelets to potent substances with opposing biological activities. The balance between the activities of these substances is important in the homeostatic interaction of the platelets and the vessel wall. The different ways of interfering with this balance and its impact in the development of thrombosis and atherosclerosis are discussed. The balance between thromboxane A2 and prostacyclin might be important in the control of the pulmonary circulation. This possibility is discussed in the light of the present evidence.
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PMID:Interrelationships between prostacyclin and thromboxane A2. 625 79

The effect of dibutyryl cyclic AMP on DNA synthesis was studied in cultured human umbilical endothelial cells and rat aortic smooth muscle cells. Dibutyryl cyclic AMP (2 X 10(-4) mol/l) inhibited DNA synthesis in both arterial cell types when they were grown in medium supplemented with whole serum or with platelet poor serum, but had no effect in the absence of serum. An effect was seen one hour after the addition of the nucleotide, and the threshold concentration was between 2 X 10(-6) and 2 X 10(-5) mol/l. These results may have relevance to the interaction of platelets and insulin with the arterial wall in the development of atherosclerosis in diabetes.
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PMID:Cyclic AMP: a potent inhibitor of DNA synthesis in cultured arterial endothelial and smooth muscle cells. 627 16

The anatomical distribution of ADPase activity in the rabbit aorta was investigated. The aortic arch and upper thoracic regions of the rabbit aorta were found to have a reduced capacity to break down ADP and also unable to further metabolise the AMP thus formed. ADPase activity progressively increased down the aorta to the abdominal regions where it was highest. The abdominal regions of the aorta together with the lower thoracic region were able to produce adenosine from ADP. These results suggest a connection between ADPase activity and the incidence of atherosclerosis in rabbits. Thus in the aortic arch and upper thoracic regions of the aorta where the incidence of the disease is higher, the ability of the vascular tissue to break down ADP is low; therefore platelet aggregation is more likely to occur in response to minimal wear and tear. Conversely, in the abdominal regions where ADPase activity is highest and the incidence of the disease is lower ADPase may play a protective role in limiting ADP-induced thrombotic response to vascular trauma.
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PMID:The anatomical distribution of ADPase activity in the rabbit aorta. 628 69

The interaction of low density lipoproteins (LDL) with cell membrane receptors is regulated by certain hormones. To test whether LDL receptor activity is influenced by cyclic AMP, the effect of dibutyryl cyclic AMP on LDL binding uptake and degradation was studied in cultured human skin fibroblasts and in rat and human arterial smooth muscle cells. Dibutyryl cyclic AMP in concentrations of 10(-3) to 10(-7)M inhibited LDL binding and degradation in fibroblasts and rat arterial smooth muscle cells, and degradation in human arterial smooth muscle cells. Inhibition of LDL receptor activity by dibutyryl cyclic AMP did not appear to be due to a non-specific toxic effect of the nucleotide. It appeared to be mediated on the affinity of the receptor for LDL rather than receptor number.
Atherosclerosis 1983 Jan
PMID:Dibutyryl cyclic AMP inhibits LDL binding in cultured fibroblasts and arterial smooth muscle cells. 630 13

Drugs that inhibit platelet activation may prevent thrombosis and atherosclerosis. The mechanism by which coumarins, heparin, calmodulin inhibitors, calcium entry blockers, drugs that interfere with cyclic AMP function and arachidonate metabolism, and several other compounds might achieve this protection, is discussed. Only a few of these drugs (acetylsalicylic acid, dipyridamole, sulfinpyrazone) have been tested for clinical efficacy in man. So far the results of these studies have revealed modest protection from infarction and other cardiovascular diseases.
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PMID:Agents interfering with the platelet-vessel wall interaction. 642 90

Endothelial cells derived from the pig aorta grow in culture with typical cobblestone morphology; after about 7 days they elongate to a more fibroblastic appearance followed by the appearance of sprouts. The sprouts can be removed by 24 h treatment with either 8-bromo-cyclic AMP or cholera toxin, when the cells revert to their original cobblestone morphology. Examination of phenotypic markers as exemplified by the collagen types synthesised in the cell layer and those released into the medium, indicated the presence of types I, III and V in the cobblestone phase; the result of sprouting and desprouting was to alter the various proportions of I, III and V in both cells and medium with the exception that type V disappeared from the medium of sprouting porcine cells. When bovine endothelial aortic cells were similarly examined, I, III and V type collagens were found in the cell layer and medium, but in vastly different proportions from those found in the pig. Sprouting and desprouting bovine endothelium produced profound changes--in the cell layer, only type V could be demonstrated, whereas I, III and V were demonstrable in the medium, albeit in differing proportions. The conclusions are firstly, that phenotypic morphological changes may or may not be accompanied by phenotypic changes in the synthesis of the various collagen markers; secondly, that the secreted collagens do not always reflect those collagens retained by the cell layer which shows sequestration of one of the collagen types; finally there is a very distinct species difference and it is not possible to extrapolate from one species to another. The ultrastructural observation that the sprouts in cultured bovine endothelium resemble everted capillaries adds value to the culture as a model system.
Atherosclerosis 1984 Jul
PMID:Phenotypic changes in morphology and collagen polymorphism of cultured bovine and porcine aortic endothelium. 646 15

Appearance of cadaverine deaminating activity in mitochondrial fractions of liver and kidney of rabbits with experimental alimentary hypercholesterolaemia was prevented by an antioxant diludin (2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine) which also decreased the abnormally elevated AMP-deaminating activity and elevated the decreased monoamine oxidase activity (substrates: serotonin, benzylamine, tyramine). In heart and brain tissues as compared with liver and kidney the impairments caused by hypercholesterolaemia and the normalizing effect of diludin were less distinct. The effects of diludin could be reproduced by nucleophylic reagents sodium thiosulphate or ascorbate. The normalization of impairments in deamination of nitrogenous compounds in hypercholesterolaemia was accompanied by improvement in morpho-physiological manifestations of atherosclerosis (injury of aortal intima, alteration in heart rhythm, changes in content of cholesterol, triglycerides and lipoproteins in blood serum). The data obtained are in agreement with the hypothesis on the significance of qualitative alteration (transformation) in catalytic properties of mitochondrial monoamine oxidases in the mechanism of impairments in deamination of nitrogenous compounds in atherosclerosis.
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PMID:[Normalization of impairments in deamination of nitrogen compounds in experimental hypercholesterolemia]. 685 40

Quantitative determination of the nucleotides AMP, ADP, ATP, GTP, NAD, NADP, 2,3-DPG and the free amino acids Lys, His, Gly, Ala, Val, Met, Phe, Tyr, Pro, Thr, Ser, Glu, Asp in erythrocytes was carried out in early and late stages of myocardial infarction. It was found that in erythrocytes, in the early stage of myocardial infarction, the concentrations of AMP, NADP and 2,3-DPG increased, whereas those of ADP, ATP, GTP and NAD decreased. In the third week of the disease the concentrations of AMP, ADP, NADP, and especially 2,3-DPG remained high, while those of ATP and GTP shifted towards the control. The concentrations of His, Gly, Ala, Val, Met, Phe, Thr and Glu increased, while those of Tyr, Ser and Asp decreased in the first stage of myocardial infarction. At the later stage of the illness (21 days) the concentrations of free amino acids returned to normal.
Atherosclerosis
PMID:Myocardial infarction. Changes in the concentrations of high-energy compounds and free amino acids in erythrocytes. 733 15

Experimental alimentary hypercholesterolaemia in rabbits caused not only a decrease in deamination of monoamines (serotonin, benzylamine, tyramine) in liver, brain, kidney and heart mitochondrial fractions but also an appearance in these fractions of a qualitatively new reactions, namely that of cadaverine deamination, which was occasionally accompanied by stimulation of AMP deamination. In mitochondrial fractions from liver tissue obtained by autopsy in cases of ischemic heart disease accompanied by atherosclerosis, as compared with the corresponding fractions from the liver of persons who died in accidents and in whom no distinct morphological manifestations of atherosclerosis could be noted, there was observed a decrease in deamination of serotonin or tyramine (by 52% and 63%), appearance of cadaverine deamination (Vmax constitutes 35% of the Vmax value for serotonin deamination in the same fraction (and stimulation) 2-fold) of AMP deamination. The impairments in deamination of the nitrogenous compounds in experimental hypercholesterolaemia and in atherosclerosis are apparently due to qualitative alteration (transformation) in catalytic properties of mitochondrial monoamine oxidases. Implications of this hypothesis for future research on treatment of atherosclerosis are discussed.
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PMID:[Mechanism of disturbances in the deamination of nitrogenous compounds in experimental hypercholesterolemia and atherosclerosis]. 733 59

Defining the mechanisms regulating the proliferation of vascular smooth muscle is necessary to better understand the pathogenesis of atherosclerosis and hypertension. In the present investigation, we examined the effects of incubation with forskolin or isoproterenol on the proliferation of cultured rat aortic smooth muscle cells. Forskolin, a direct activator of adenylate cyclase, and isoproterenol, a beta-adrenergic agonist, increased intracellular cyclic AMP levels in a concentration-dependent manner, subsequent to a 5-min exposure. Isobutylmethylxanthine at 100 microM attenuated epidermal growth factor stimulated DNA synthesis by 35% without affecting intracellular cyclic AMP levels. Forskolin dose-dependently augmented this inhibition. In contrast, a 24-h exposure of cells to isoproterenol resulted in a biphasic effect on growth factor stimulated thymidine incorporation. Both forskolin and isoproterenol attenuated thymidine incorporation to the same degree up to 12 h poststimulation, the onset of S phase. By 16 h poststimulation, [3H]thymidine incorporation in smooth muscle cells treated with isoproterenol was significantly enhanced by 50%, whereas forskolin treatment continued to attenuate DNA synthesis by 40%. Somewhat surprisingly, this disparity in effect on DNA synthesis was evident in spite of heterologous desensitization to rechallenge by either forskolin or isoproterenol subsequent to a 24-h incubation with either drug. These results suggest that the isoproterenol enhancement of epidermal growth factor stimulated DNA synthesis in rat aortic smooth muscle cells may be cyclic AMP independent.
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PMID:Forskolin and isoproterenol effect discrete responses on epidermal growth factor induced DNA synthesis in aortic smooth muscle cells. 751 81


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