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)

The effect of low-density lipoprotein, serotonin and low-density lipoprotein plus serotonin on platelet aggregation (measured ex vivo in plasma) was studied in 28 normotensive subjects (15 non-smokers, 13 smokers) and 15 previously untreated non-smoking patients with essential hypertension. Low-density lipoprotein alone had no platelet-activating effect. Serotonin-induced platelet aggregation was enhanced by low-density lipoprotein in both the normotensive and the hypertensive subjects. The platelet response to low-density lipoprotein plus serotonin was higher in the smokers than in the non-smokers; it was also higher in the hypertensive patients than in the normotensive controls. We conclude that low-density lipoprotein activates platelets in plasma via an interaction with a serotonergic mechanism. Low-density lipoprotein amplifies the serotonin-induced platelet aggregation (normally reversible), making it irreversible. A higher platelet response to low-density lipoprotein plus serotonin in patients with essential hypertension may be of pathophysiological relevance in respect to the thrombovascular lesions accompanying hypertension and/or atherosclerosis.
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PMID:Low-density lipoprotein amplifies the platelet response to serotonin in human plasma. 263 5

Endothelial cell (EC) injury and the response of EC and smooth muscle cells (SMCs) to injury contribute to the pathophysiology in patients with vascular disease and atherosclerosis. Since platelets have been suggested to play an important role in modulating vascular injury, the present study was undertaken to examine the influence and mechanism of action of individual platelet factors on bovine aortic EC and SMC migration using an in vitro wound assay system. Serotonin decreased EC proliferation and reduced EC migration 21 +/- 1% (p less than 0.005), which was attenuated by imipramine. Transforming growth factor-beta reduced EC proliferation and decreased EC migration 52 +/- 3% (p less than 0.005). Norepinephrine increased EC proliferation but decreased EC migration 26 +/- 2% (p less than 0.005), which was abolished by phenoxybenzamine. Histamine increased EC proliferation but reduced EC migration 29 +/- 2% (p less than 0.005), which was attenuated by diphenhydramine. Platelet-derived growth factor decreased EC proliferation and decreased EC migration 40 +/- 2% (p less than 0.005). In contrast, serotonin increased SMC proliferation and increased SMC migration 31 +/- 2% (p less than 0.005), which was abolished by ketanserin. Transforming growth factor-beta increased SMC migration 35 +/- 5% (p less than 0.005). Norepinephrine increased SMC proliferation and increased SMC migration 43 +/- 4% (p less than 0.005), which was abolished by propranolol. Histamine increased SMC proliferation and increased SMC migration 38 +/- 3% (p less than 0.005), which was abolished by cimetidine. Platelet-derived growth factor increased SMC proliferation and increased SMC migration 40 +/- 3% (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of platelet factors on migration of cultured bovine aortic endothelial and smooth muscle cells. 279 Dec 19

Blood serotonin levels have been measured by spectrofluorometry in 145 patients with various manifestations of acute disorders of the cerebral circulation (ADCC): with ischemic stroke, cerebral hypertensive crises, transient impairments of the cerebral circulation, and with circulatory encephalopathy (DE) in the presence of arterial hypertension combined with atherosclerosis. In ADCC patients the blood serotonin has been measured 7 times, in DE ones 3 times. This level has been found changed in the patients with ischemic stroke and with cerebral hypertensive crises for a long time after the cerebral circulation impairment. Serotonin levels correlated with the condition severity and course in ADCC and DE. The vestibulocerebellar syndrome in DE has been treated more effectively, particularly with trental. The blood serotonin level may be regarded as a prognostic criterion of the disease outcome and of the treatment efficacy.
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PMID:[Dynamics of blood serotonin contents in acute disorders of cerebral circulation and circulatory encephalopathy]. 279 19

In monkeys with early and advanced atherosclerosis, we examined responses to the three major vasoactive agonists that are released when platelets aggregate. Measurements were obtained in normal cynomolgus monkeys and in monkeys fed an atherogenic diet for 4 +/- 1, 9 +/- 1, and 19 +/- 1 months (mean +/- SEM). Morphometry of femoral and iliac arteries indicated that 4 months of atherogenic diet produced only slight intimal thickening, 9 months produced early lesions, and 19 months produced approximately 5-10 fold greater intimal proliferation than did 9 months of atherogenic diet. Serotonin and adenosine 5'-diphosphate (ADP), which are endothelium-dependent agonists, and adenosine and phenylephrine, which are endothelium-independent agonists, were injected intra-arterially into the perfused hind limb. Thromboxane A2 analogue U46619 also was studied. Vasoconstrictor responses to serotonin were potentiated, and vasodilator responses to ADP were impaired by early and advanced atherosclerosis. In contrast, vasoconstrictor responses to phenylephrine and vasodilator responses to adenosine were similar in all groups. Vasoconstrictor responses to U46619 were potentiated by advanced atherosclerosis. Thus, vascular responses to serotonin, ADP, and thromboxane A2 are altered by atherosclerosis in a direction that would favor vasoconstriction when platelets aggregate. Furthermore, because responses to endothelium-dependent agonists are altered, these data suggest that endothelium is dysfunctional in early atherosclerosis. These findings may explain, in part, the propensity for exaggerated vasoconstriction even in arteries with minimal atherosclerotic lesions.
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PMID:Effect of early and advanced atherosclerosis on vascular responses to serotonin, thromboxane A2, and ADP. 291 93

Vasoconstrictor responses to serotonin and norepinephrine were examined in: normal cynomolgus monkeys, atherosclerotic monkeys that were fed atherogenic diet for 3-5 years and hypercholesterolaemic but non-atherosclerotic monkeys that were fed atherogenic diet for 4-5 months. Serotonin decreased total hindlimb resistance in normal and hypercholesterolaemic monkeys, but increased total resistance in atherosclerotic monkeys. There was a greater than 10-fold increase in constrictor responses of large arteries to serotonin in atherosclerotic compared with normal and hypercholesterolaemic monkeys. In contrast, responses to norepinephrine were not increased in atherosclerotic monkeys. Thus, atherosclerosis greatly potentiates constrictor responses to serotonin in large arteries of the limb. This potentiation appears to be somewhat selective for serotonin, as it is not observed with norepinephrine.
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PMID:Potentiation of vasoconstrictor responses to serotonin in the limb of atherosclerotic monkeys. 293 10

Chronic treatment of rats with dexfenfluramine decreased the concentrations of circulating corticosterone, fatty acid, glycerol, and triacylglycerol after feeding a test load of fructose. It also decreased the rise in adrenalin in the blood of rats that were anaesthetized with urethane. These effects of dexfenfluramine probably result from changes in the metabolism of 5-HT in the CNS and consequent alterations in hormonal balance. It is proposed that the long-term metabolic effects of dexfenfluramine could be explained by a decrease in the effectiveness of stress hormones (e.g., glucocorticoids, corticotropin, catecholamines, glucagon) in regulating metabolism since these hormones antagonize many of the actions of insulin. This hypothesis also identifies the possibility that the ability of dexfenfluramine to decrease an exaggerate stress response could alleviate some of the potential risk factors associated with atherosclerosis including obesity and maturity onset diabetes.
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PMID:Metabolic and hormonal effects of dexfenfluramine on stress situations. 318 Jan 10

Atherosclerosis may be important in the modulation of arterial vasoreactivity and coronary artery flow. Since the endothelium is reduced or absent in atherosclerosis, drug effects are enhanced or modulated. To examine this hypothesis, vasoreactivity induced by serotonin (5-HT) was studied in isolated, perfused, and pharmacologically responsive normal and atherosclerotic human coronary arteries obtained within five hours post mortem. In this model, flow was maintained through the vessels and the effects of vasospasm and vasorelaxation on decreasing and increasing flow respectively were measured. Vessels 3 cm long and approximately 1.5 mm in internal diameter were dissected free and perfused at constant pressure (30 mm Hg) with oxygenated Krebs bicarbonate solution. 5-HT was introduced in the perfusate at 10(-5) M final concentration as a pulse of 100 ml followed by a 1-l washout with drug-free solution. Flow rate and total flow were measured. Normal and atherosclerotic coronary arteries showed peak reductions in flow rate of 22% and 92% respectively, while the times to peak reduction of flow averaged 6 and 4 min and the times to 50% relaxation averaged 13 and 24 min. Ultrasound imaging showed that heavily atherosclerotic regions with extensive focal plaque maintained the induced spasm for a longer period than regions with less disease within the same vessel. Silver nitrate staining showed that these heavily atherosclerotic regions were devoid of endothelium. Thus, atherosclerotic human coronary arteries show a larger magnitude of spasm which persists for a longer period of time as compared to normal coronaries.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasoreactivity in isolated perfused atherosclerotic human coronary arteries. 322 33

A recent resurgence of interest into the role of platelets in the pathogenesis of ischaemic syndromes associated with atherosclerosis, and the development of new antagonists for major platelet products, has led to a broad range of studies into the mechanisms by which serotonin, and other factors released by platelets, may contribute to ischaemia. Serotonin influences large arteries in vivo to induce constriction through an action on the 5-HT2 serotonin receptor. Several studies now show, at least for the limb blood supply, that collateral arteries after major artery occlusion are extremely sensitive to serotonin acting on the 5-HT2 serotonin receptor. Preliminary studies on platelet activation secondary to endothelial damage induced by mechanical abrasion in the rabbit with collateral limb vessels indicate that vasoactive quantities of serotonin are, indeed, released and that the response of the collateral vessels is reversed, at least in part, by ketanserin. Preliminary evidence also indicates that simultaneous blockade of serotonin and thromboxane achieves a greater effect than blocking either alone, following platelet activation.
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PMID:Serotonin and the peripheral circulation. 345 2

Diet-induced atherosclerosis in primates impairs vasodilator responses and greatly potentiates vasoconstrictor responses to serotonin. Serotonin may play an important role in the pathogenesis of vasospasm. In diet-induced regression of atherosclerosis, intimal lesions are reduced, but maximal vasodilator responses do not improve, perhaps because of vascular fibrosis. Our goal was to determine whether dietary treatment of atherosclerosis reverses the augmented vasoconstrictor responses to serotonin and thus might reduce susceptibility to vasospasm. Normal cynomolgus monkeys, atherosclerotic monkeys, and atherosclerotic monkeys that were given a normal (regression) diet for 18 months were studied. Morphometric studies indicated that the regression diet reduced lesions in the iliac and femoral artery since intimal area was reduced by about 50%. In the hind limb perfused at constant flow, residual resistance during maximal vasodilatation produced by infusion of adenosine tended to be greater in atherosclerotic monkeys than in normals and failed to improve in regression monkeys. In contrast, vasoconstrictor responses to serotonin were greatly potentiated in atherosclerotic monkeys and were restored to normal in regression monkeys. Serotonin (20 micrograms i.a.) decreased hind limb resistance (in mm Hg/ml/min) 0.34 +/- 0.06 (mean +/- SE) in normal monkeys, increased resistance 0.58 +/- 0.17 in atherosclerotic monkeys (p less than 0.05 vs. normal), and decreased resistance 0.70 +/- 0.15 in regression monkeys (p less than 0.05 vs. atherosclerotic). Thus, dietary treatment of atherosclerosis abolishes augmented vasoconstrictor responses to serotonin. It is proposed that treatment of atherosclerosis may be beneficial, even when vasodilator responses fail to improve, by reducing susceptibility to serotonin-induced vasospasm.
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PMID:Dietary treatment of atherosclerosis abolishes hyperresponsiveness to serotonin: implications for vasospasm. 362 97

Serotonin, which is released when platelets aggregate at carotid lesions, may contribute to cerebral ischemia. Our goal was to test the hypothesis that dietary treatment of atherosclerosis reverses the augmented cerebral vasoconstrictor response to serotonin. We studied normal cynomolgus monkeys, atherosclerotic monkeys, and atherosclerotic monkeys that were fed a normal (regression) diet for 18 months. Morphometric studies indicated that the regression diet reduced intimal area in the carotid arteries by about 50-75%. Cerebral blood flow was measured with microspheres, and microvascular pressure was measured with a micropipette in pial arteries that were approximately 300 micron in diameter. Values for cerebral blood flow and arteriolar pressure were used to calculate resistance of large cerebral arteries (greater than 300 micron diameter). Infusion of serotonin produced a modest increase in the resistance of large cerebral arteries in normal monkeys. Vasoconstrictor responses to serotonin were increased more than fivefold in atherosclerotic monkeys. The major finding of the study is that dietary treatment of atherosclerosis abolishes augmented cerebral responses to serotonin.
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PMID:Cerebral vasoconstrictor responses to serotonin after dietary treatment of atherosclerosis: implications for transient ischemic attacks. 368 79


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