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)

Cellular components of the bronchovascular barrier have been studied in human lungs obtained after death of some patients with acute and chronic lung inflammatory diseases, hypertonic disease, atherosclerosis and chronic glomerulonephritis. Certain oxidative-reductive and hydrolytic enzymes, including NAD-, NADP- diaphorases, lactic dehydrogenase, acid and alkaline monophosphoesterase, ATP-ase, adenylate cyclase and nonspecific esterase were evaluated quantitatively after the histochemical processing of the specimens for the above reactions. Correlation analysis was performed for the bronchial epithelium, endotheliocytes, lymphocytes, plasma and mast cells, as well as macrophages and polymorphonuclear leucocytes. The results showed that there was a significant shift in some of the measured enzymic activities. Moreover, the correlations between different quantitative data were noted and these correlations changed with age. The increase in "rigidity" of the correlations in the elements of the bronchovascular barrier has been demonstrated during the process of ageing.
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PMID:Functional morphology of the bronchovascular barrier of the human lungs during various age periods. 214 10

A method is described for the quantification of vascular smooth muscle cell growth from individual explants of contractile rabbit aortic tunica media. The precision of the method probably depends on regular explant geometry (1-mm squares) and pooling sufficient explants. Serum-induced growth was quantified by measurements of ATP concentration, incorporation of [3H]thymidine and DNA concentration. The possible effects of endogenous vasodilator agents on growth were investigated by using lipid soluble analogues of their second messengers, namely 8-Br-cAMP and 8-Br-cGMP, which are known to relax rabbit aortic strips. Cell growth was inhibited concentration-dependently by 8-Br-cAMP but not 8-Br-cGMP (0.01-1 mM). The effect of 8-Br-cAMP was reversible, and also occurred when addition was delayed until after growth had commenced. The results imply that endogenous vasodilators such as prostacyclin, adenosine and adrenaline, which increase cAMP concentration, may normally suppress smooth muscle cell growth, whereas nitric oxide and atriopeptins, which increase cGMP concentration, may not.
Atherosclerosis 1990 May
PMID:Serum-induced proliferation of rabbit aortic smooth muscle cells from the contractile state is inhibited by 8-Br-cAMP but not 8-Br-cGMP. 216 52

The effects of varying degrees of atherosclerotic plaque on vascular responsiveness in aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits and New Zealand White (normal cholesterolemic) rabbits were studied. Ring segments from the aortic arch and thoracic aorta were mounted in organ chambers for isometric tension recording and measurement of endothelium-derived relaxing factor. WHHL rabbits were divided into three groups according to age: group 1, 3-5 months; group 2, 6-9 months; and group 3, 12-14 months. Atherosclerotic changes (expressed as a percent of total surface area) in the aortic arches in groups 1, 2, and 3 were 11 +/- 3% (mild), 28 +/- 6% (moderate), and 54 +/- 8% (severe) respectively; only occasional plaques were present in the thoracic aorta in all groups. Maximal contractions elicited with phenylephrine progressively decreased with increasing degrees of atherosclerotic plaque. Contractions evoked by histamine were augmented in all groups of WHHL rabbits when compared with controls, whereas those to serotonin were augmented only in vessels with mild atherosclerosis. As the severity of the intimal lesions increased, endothelium-dependent relaxations to acetylcholine, ATP, and calcium ionophore A23187 progressively decreased. Endothelium-independent relaxation to nitroglycerin was virtually complete in all segments. However, vessels with severe atherosclerosis were less sensitive to this agent as illustrated by a significant increase in the ED50 value. Scanning electron microscopy revealed a predominant loss of endothelial cells in the central regions of fibrous plaques. Thus, in WHHL rabbits, hypercholesterolemia and atherosclerosis result in an increased responsiveness of vascular smooth muscle to histamine and serotonin. Endothelium-mediated relaxation of vascular smooth muscle is reduced with the progression of atherosclerosis primarily due to a loss of endothelial cells.
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PMID:Vascular reactivity during the progression of atherosclerotic plaque. A study in Watanabe heritable hyperlipidemic rabbits. 231 89

The effect of chronic oral defibrotide on platelet function, vascular PGI2 generation, atherosclerotic plaque formation and serum lipids was studied in rabbits. The animals were fed for 4 months a standard laboratory diet (150 g/day) with or without defibrotide (60 mg/kg/day) or a cholesterol-rich (1%) diet with or without defibrotide. Defibrotide significantly reduced the platelet reactivity ex vivo against collagen and ADP. This included a reduced aggregation response, thromboxane release and ATP secretion. Furthermore, the inhibition of platelet function and stimulation of platelet cAMP by iloprost, were significantly improved by defibrotide treatment. This was associated with an increased number of prostacyclin binding sites and enhanced PGI2 affinity in platelet membranes from these animals. Bradykinin stimulated PGI2 generation of segments of the thoracic aorta about 2-fold above control in both normo- and hypercholesterolemic rabbits. There was no difference in basal values between these groups but a more than 2-fold increase in either group by defibrotide treatment. Atherosclerotic plaque formation, determined by a subjective score, was found to be significantly reduced by defibrotide although the compound did not alter serum cholesterol levels. The data suggest potent and potentially valuable antiatherosclerotic effects of oral defibrotide: (i) normalization of platelet function by reduction of platelet hyperreactivity and improvement of the sensitivity towards prostacyclin, and (ii) stimulation of vascular PGI2 production.
Atherosclerosis 1989 Nov
PMID:Stimulation of vascular prostacyclin and inhibition of platelet function by oral defibrotide in cholesterol-fed rabbits. 251 13

We performed an in vitro study to assess injury to vascular endothelial cells by platelets. Cultured endothelial cells isolated from fetal bovine aorta were used. Addition of human platelets, activated by collagen or lysed by sonication, to the culture dish resulted in dose- and time-dependent damage to the cells as estimated by [3H]adenine release. Analysis of [3H]adenine nucleotides by thin-layer chromatography on PEI-cellulose revealed decreased intracellular ATP content in the cells treated with platelet lysate. The medium contained AMP and adenosine, the latter increasing following the treatment of the cells. Of the substances released by the activated platelets, thromboxane A2 (TxA2) and serotonin caused cell damage. Platelet-derived growth factor (PDGF), however, did not damage the endothelial cells up to a concentration of 200 ng/ml. Pretreatment of the cells with methysergide (10(-6) M) or ONO 3708 (10(-5) M), a TxA2 antagonist, only partially prevented the damage, while ZK 36374 (10(-6) M), a prostacyclin analog, and 3-isobutyl-1-methylxanthine (IBMX; 10(-3) M), a phosphodiesterase inhibitor, potently inhibited injury. We conclude that the substances released from activated platelets may injure endothelial cells in an additive or synergistic manner and that agents which produce effects that elevate cyclic AMP levels may protect the cells from damage induced by the platelets.
Atherosclerosis 1989 Apr
PMID:In vitro study of vascular endothelial injury by activated platelets and its prevention. 254 23

Functional and metabolic parameters of thoracic aorta from Watanabe heritable hyperlipemic (WHHL) rabbits (aged 11-14 months) were investigated in vitro. The aortic preparations, normally responsive to noradrenaline, showed a diminished response to the endothelium-dependent agent, acetylcholine, in comparison with control preparations from age-matched New Zealand rabbits (maximal relaxation: 33 +/- 4% in WHHL vs. 52 +/- 2% in controls: P less than 0.005). ATP relaxant effect (only partially endothelium-dependent) was unimpaired in WHHL aorta, and it was much higher than in controls (maximal response: 63 +/- 6% vs. 37 +/- 3%, respectively; P less than 0.005). The response to NaNO2, an endothelium-independent relaxant, was unchanged in WHHL aortas. Acetylcholine-induced response was found to be inversely related to the degree of total cholesterol infiltration in aorta (r = -0.62, P less than 0.05). No correlation was observed between either total serum cholesterol or triglycerides and ACh-induced response. Furthermore, the concentration of adenine nucleotides and nucleosides in the aortic tissue of WHHL rabbits was lower than in controls, indicating a loss of energy balance. The results indicate a functional damage induced by genetic hyperlipidemia on endothelium-dependent relaxation and an impairment of energy-rich phosphate metabolism of the aortic wall. The relationship between functional and metabolic parameters is not yet clarified.
Atherosclerosis 1989 Dec
PMID:Endothelium-dependent relaxation, cholesterol content and high energy metabolite balance in Watanabe hyperlipemic rabbit aorta. 261 Jul 24

To clarify whether the inverse relation between habitual fish consumption and cardiovascular mortality in the Dutch town of Zutphen could be explained by changes in platelet function or fibrinolysis, 40 healthy elderly men were selected from the Zutphen study population on the basis of their fish consumption over the last 26 years. In the high-fish group (n = 25) fish consumption was on average 33 g per person per day; in the low-fish group (n = 15) it was on average 2 g per person per day. This difference was reflected by significant differences in the concentrations of timnodonic acid (20:5n - 3) and cervonic acid (22:6n - 3) in the serum phospholipids of the participants. Between both groups no significant differences were observed in cutaneous bleeding time, platelet number, and collagen-induced platelet aggregation and ATP-release in whole blood. The same holds for the actual as well as the potential thromboxane B2 formation of activated platelets and for the activity of the plasminogen activator inhibitor. For most of the platelet-related variables a trend was found for a lower activity in the high-fish group. Therefore changes in platelet function might not explain, but may have slightly contributed to the inverse relationship between coronary heart disease and fish consumption, as observed in Zutphen.
Atherosclerosis 1989 Feb
PMID:Habitual fish consumption, fatty acids of serum phospholipids and platelet function. 271 61

Cultured human endothelial cells synthesize prostacyclin (PGI2), a potent inhibitor of platelet function, when stimulated with histamine, bradykinin, or ATP. Paradoxically, we report that these agonists also induced the rapid and sustained synthesis of platelet-activating factor (PAF) by endothelial cells. In fact, the synthesis of this potent activator of platelets and neutrophils was induced by stimulation of the same receptor subtype that induced PGI2 synthesis: stimulation of a histamine H1 or a bradykinin B2 receptor induced both PAF and PGI2 synthesis. However, two physiologically important differences exist between the production of PAF and PGI2 by endothelial cells. The synthesis of PGI2 proceeded for only 7.5 min before the abrupt termination of synthesis, whereas the synthesis of PAF was clearly detectable even 45 min after stimulation. Although maximal accumulation of PAF occurred after 10-15 min of stimulation, the prolonged synthesis resulted in the presence of PAF for up to 1 h after stimulation. Secondly, whereas PGI2 was released from the cell monolayer, PAF remained cell-associated without significant release to the external medium. Endothelial cell-generated PAF, therefore, does not function as a hormone. The prolonged association of this potent activator of platelets and neutrophils with endothelial cells may mediate some of the inflammatory properties of histamine and bradykinin. It may also be a factor in the formation of a thrombogenic vascular surface, an event suggested to play a primary role in the pathogenesis of thrombosis and atherosclerosis.
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PMID:Cultured endothelial cells synthesize both platelet-activating factor and prostacyclin in response to histamine, bradykinin, and adenosine triphosphate. 286 64

Myocardial ischaemia results from complex interrelated processes involving progression of atherosclerosis, thrombosis, coronary spasm, platelet aggregation and local release of products from the arachidonic acid cascade. Endothelium-dependent responsiveness contributes to the local regulation of coronary blood flow, and the presence of endothelial damage may result in enhanced contraction of the smooth muscle. Drugs which have been used for the treatment of angina pectoris are able to reduce myocardial oxygen consumption. This concept will further be developed in the near future with beta-blocking agents with vasodilating properties, potent long acting nitrates (nicorandil), bradycardic agents (AQA 39 or AS-AH 208), and new calcium antagonists. However, future prospects in the treatment of angina pectoris include: drugs modifying the arachidonic acid cascade by increasing synthesis or release of prostacyclin (nafazatrom) or decreasing prostacyclin degradation (almitrine), or blocking thromboxane A2 synthetase (dazoxiben) or thromboxane A2 receptors (BM 13177) or, blocking the lipoxygenase pathway (nafazatrom) or prostacyclin analogues (iloprost); more clot-specific thrombolytic agents and new oral anticoagulant drugs; free-radical scavengers such as superoxide dismutase, catalase or peroxidase and drugs inhibiting xanthine-oxidase; anti-platelet drugs such as ticlopidine which blocks the fibrinogen receptors of platelets; drugs preventing the progression of atherosclerosis lesions such as nifedipine or verapamil in animals fed high-lipid diets; drugs which could modify myocardial metabolism during ischaemia. In this context, trimetazidine acts through prevention of ischaemia-induced decrease in ATP cellular storages, inhibition of potassium leak, decrease in free-radical production and thromboxane A2 synthesis and increase in prostacyclin synthesis. These new concepts provide an important contribution to the understanding of the pathophysiology of myocardial ischaemia. This explains the considerable development of pharmacological research for new agents in the treatment of angina pectoris.
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PMID:[Treatment of angina pectoris. New perspectives]. 294 45

The effect of a thromboxane receptor antagonist (Daltroban, BM 13.505) on platelet function, vascular PGI2 formation and the severity of atherosclerotic lesions was studied in rabbits, fed for 4 months a cholesterol rich (1%) diet. Daltroban (10 mg/kg x day) significantly antagonized the hypercholesterolemia induced enhanced platelet aggregability, thromboxane formation and ATP secretion. The vascular PGI2 biosynthesis ("basal" or bradykinin stimulated), the number of PGI2 receptors on platelet membranes and the atherosclerotic plaque formation in the aorta were not affected by Daltroban. We suggest that in addition to a reduction of platelet hyperreactivity, protection of the vessel wall appears to be required for prevention of atherosclerosis in this model.
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PMID:Beneficial effects of a thromboxane receptor antagonist (BM 13.505) on platelet hyperreactivity and thromboxane formation in cholesterol-fed rabbits. 307 72


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