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

In this study hemodynamic and morphometric consequences of atherosclerosis were examined in cynomolgus monkeys. We tested the hypothesis that atherosclerosis augments cerebral vasoconstrictor responses to serotonin. We studied 8 normal and 8 atherosclerotic monkeys, which were fed an atherogenic diet for 17 months. Morphometric studies indicated marked intimal proliferation of extracranial carotid arteries, with only modest reduction in the vascular lumen, as atherosclerotic lesions were displaced outward. Cerebral blood flow was measured with microspheres and microvascular pressure was measured with a micropipette in pial arteries approximately 350 microns diameter. Intracarotid infusion of serotonin reduced microvascular pressure, which indicates constriction of large arteries upstream, but cerebral blood flow did not decrease. Serotonin produced a 2-fold greater reduction in cerebral microvascular pressure in atherosclerotic monkeys than in normal monkeys. Intracarotid histamine increased flow and hypocapnia reduced flow in both normal and atherosclerotic monkeys, without altering cerebral microvascular pressure. We conclude: First, atherosclerosis potentiates constrictor responses to serotonin in large cerebral arteries. Because platelets release serotonin when they aggregate, augmentation of responses by atherosclerosis may have implications for cerebral vascular responses during aggregation of platelets at carotid lesions. Second, despite marked proliferation of intima, atherosclerotic lesions are displaced outward during a prestenotic phase of the disease, so that the lumen is relatively well preserved.
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PMID:Effects of atherosclerosis on cerebral vessels: hemodynamic and morphometric studies. 381 Jul 23

In order to further characterize the modulation of the ADP-induced aggregation of gel-filtered human platelets by beta 2-glycoprotein-I (beta 2-G-I), the influence of this glycoprotein upon the serotonin (5-HT) release during aggregation was measured. The following results were obtained: beta 2-G-I completely inhibits the 5-HT release during ADP-induced platelet activation. The inhibition is correlated with the inhibition of the second wave of the ADP-induced aggregation. This effect of beta 2-G-I is not dose-dependent and appears above a threshold concentration of 0.1-0.15 mg/ml in the assay. The specificity of the beta 2-G-I interaction with the ADP-activation is supported by results obtained with collagen or thrombin as aggregating agents. In these cases neither the aggregation nor the release is influenced by the glycoprotein. In respect to the results obtained, beta 2-G-I is a potent candidate to be a modulator of ADP-induced platelet activation in vivo.
Atherosclerosis 1987 Feb
PMID:Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation. 382 75

Uptake by the arterial wall of plasma constituents has considerable clinical implication; thus, uptake of low density lipoprotein (LDL) plays an important role in the development of atherosclerosis. Serotonin and other vasoactive material may result in changes in the arterial wall leading to increased uptake of albumin or low density lipoprotein. This study was conducted to determine the effect of serotonin (10(-5)M 5-hydroxytryptamine) and serotonin-induced arterial constriction on albumin and low density lipoprotein uptake rates in perfused rabbit femoral arteries. The results show that the presence of serotonin inhibits the rate of uptake of both albumin and LDL. The effect on albumin uptake does not have a direct dose response dependence and is linearly dependent on transmural pressure. In contrast, LDL uptake rates are only slightly affected by pressure. Thus, albumin and LDL uptake processes appear to be due to separate mechanisms.
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PMID:Effect of serotonin on albumin and low density lipoprotein uptake in perfused rabbit femoral arteries. 649 51

We examined effects of hypercholesterolemia and atherosclerosis on vasoconstrictor responses to norepinephrine and serotonin. Responses were compared in normal, atherosclerotic, and hypercholesterolemic but non-atherosclerotic cynomolgus monkeys. The hindlimb was perfused at constant flow so that changes in perfusion pressure indicated changes in vascular resistance. We measured the pressure gradient from the iliac to the dorsal pedal artery so that responses of the large artery segment could be determined. Serotonin decreased total hindlimb resistance in normal and hypercholesterolemic 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 monkeys, compared with normal and hypercholesterolemic monkeys. In contrast, we found that vasoconstrictor responses to norepinephrine are normal in atherosclerotic monkeys and increased in hypercholesterolemic monkeys prior to development of atherosclerosis. Hypercholesterolemia augmented responses of small vessels to norepinephrine. We conclude that, during early stages of hypercholesterolemia in cynomolgus monkeys, vasoconstrictor responses to norepinephrine are increased in small vessels. At a later stage, as atherosclerosis develops, responses to norepinephrine return to normal, but vasoconstrictor effects of large arteries to serotonin are greatly potentiated.
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PMID:Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys. 673 66

A lot of over 60 atherosclerotics with clinical manifestations of senile depressive illness was studied comparatively with a lot of subjects of the same age with essential arterial hypertension (EAH). As concerns the behaviour of the catecholamine content in CSF and blood, the total catecholamines are approxiately equal in the two lots, but with a clear difference of the catecholamine fractions. The CSF catecholamines behaviour in old atherosclerotics is characterized by the presence of increased values of noradrenaline (NA) and of adrenaline (A), with increased statistical significance, but without modifications of the adrenaline percentage (A %) from the total catecholamines, comparatively to the values found in normal subjects. The serotonin (5-HT) content of the CSF in men with atherosclerotic senile depressive illness was lower even than in subjects with coronary atherosclerosis. In atherosclerosis protides modifications precede the histologic changes. In CSF, GLU, ALA, TYR increase in old subjects. In blood, GLU, ALA, TYR, HIS, LEU, SER increase in the same subjects. ARG decreases with age. THR is higher in men than in women. In the urine of all the men as well as of all the women of more than 60 years, GLN and ALA have increased values. LYS increases with age. GLN and ARG are higher in men than in women.
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PMID:Pattern of the cerebrospinal fluid (CSF) and blood biogenic amines and of the CSF, blood and urine amino acids as pathogenetic ground of the senile depressive illness. 677 91

The effects of different kinds of acute stress on collagen-induced whole blood platelet aggregation and fibrinolysis in relation to blood serotonergic measures were studied. In rats water-immersion restraint stress resulted in a shortening of euglobulin clot lysis time (ECLT), an increase in tissue plasminogen activator (tPA) activity with a concurrent fall in its inhibitor activity. Footshock caused rather a suppression in fibrinolysis with a prolongation of ECLT and a decline in tPA activity as well as a reduction in whole blood platelet aggregation induced by collagen. Serotonin (5-HT) level, a marker of a severity of stress, increased after footshock application with a concomitant rise in its major metabolite-5-hydroxyindoleacetic acid (5-HIAA). This indicates an enhanced 5-HT metabolism. Following water-immersion restraint stress 5-HT and 5-HIAA levels did not differ from controls. In both groups of stressed animals an inverse correlation between tPA activity and blood serotonin was observed. Our data indicate that these types of stress may influence either fibrinolysis or peripheral serotonergic mechanism in different ways. Acute and severe stress such as footshock by causing an impairment in fibrinolysis and a rise in 5-HT may contribute to the pathogenesis of thrombosis and henceforth to the development of atherosclerosis.
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PMID:Stress-dependent changes in fibrinolysis, serotonin and platelet aggregation in rats. 751 40

Using ELISA method, the sera from 17 patients with atherosclerosis and 13 normal controls were examined for ganglioside- and serotonin-reactive antibodies. Gangliosides from human liver (GM31) and human aorta (GM3a) as well as GM2, GM1, GT1b, human brain cerebrosides and the BSA-serotonin conjugate (5-HT) were used as antigens. A group of patients showed statistically significant higher levels of anti-GM31 (82%) and anti-5-HT (71%) as compared to the control group. Taking into account the identical fatty acid composition of GM3 from human liver and platelets, one can assume that antibodies are produced against blood clot gangliosides in atherosclerotic patients' sera. This conclusion is supported by a high correlation (r = 0.06, p < 0.01) between the level of antibodies to 5-HT and GM31 in the sera of all patients. The sera of three patients with the highest content of antibodies to GM31 were shown to contain antibodies to GM3a and GT1b which were absent in control sera. No reaction with brain cerebrosides or GM1 and GM2 was detected in the sera of the examined persons. The differences in sera reactions with GM31 and GM3a can be explained as resulting from differences in the chain length of fatty acid residues of the ceramide moiety of gangliosides. The data obtained confirm the fact that antibodies to aorta gangliosides appear in the sera of atherosclerotic patients. Thus, the formation of atherosclerotic plaques leading to platelet activation, clot formation and ganglioside accumulation in aortic cells increase the levels of anti-ganglioside GM3 antibodies.
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PMID:[Autoantibodies to ganglioside GM3 and serotonin in blood serum in atherosclerosis]. 766 97

Among other mediators, platelet-derived serotonin (5-HT) may contribute to thromboembolic complications of atherosclerosis. We determined whether long-term oral treatment with the 5-HT2 antagonist naftidrofuryl (NAF, 50 mg/kg daily for 12 weeks) alters platelet function in cholesterol-fed (1%) rabbits. Hypercholesterolemia resulted in marked platelet hyperreactivity to collagen and ADP. This included increased aggregation, ATP secretion, and thromboxane formation; e.g., collagen-induced (1.2 micrograms/ml) platelet aggregation was stimulated to 210 +/- 10 mm/30 s in cholesterol-fed rabbits as compared with 108 +/- 9 mm/30 s in rabbits fed a standard diet (p < 0.05). Inhibition of ADP-stimulated platelet activation by the prostacyclin mimetic iloprost was significantly reduced. NAF did not reduce plasma cholesterol in hypercholesterolemia, but prevented enhanced platelet aggregation, thromboxane formation, and ATP secretion. NAF treatment significantly reduced collagen-induced (1.2 micrograms/ml) aggregation to 81 +/- 20 mm/30 s in these animals (p < 0.05). NAF also inhibited functional desensitization of platelets to iloprost, but did not alter the impaired binding of [3H]iloprost to platelet membranes in hypercholesterolemic animals. NAF also did not change any of these parameters in normocholesterolemic rabbits. These data suggest beneficial effects of NAF on platelet hyperreactivity in experimental hypercholesterolemia which may also be relevant for its clinical use.
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PMID:Oral naftidrofuryl prevents platelet hyperreactivity ex vivo and inhibits functional desensitization to prostacyclin in hypercholesterolemic rabbits. 767 70

We have studied the relationships between whole blood and plasma serotonin (5-hydroxytryptamine, 5-HT), its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) and serum lipids, platelet aggregation in the whole blood and in the platelet-rich plasma (PRP), and some fibrinolytic parameters in monkeys. Plasma 5-HT was found to be positively related to 5-HT- and ADP-induced platelet aggregation, tissue plasminogen activator (tPA) activity, serum cholesterol and LDL-cholesterol, whereas 5-HT in cerebrospinal fluid correlated inversely with serum cholesterol. Plasminogen activator inhibitor (PAI) activity was positively related to LDL. Euglobulin clot lysis time was related to both tPA and PAI activities. The significance of these findings and the possible role of 5-HT in atherogenesis and hemostasis are discussed.
Atherosclerosis 1994 Sep 30
PMID:Correlations between platelet aggregation, fibrinolysis, peripheral and central serotonergic measures in subhuman primates. 775 51

Hypersensitivity to vasoactive stimuli, a common finding in atherosclerotic arteries, is thought to play an important role in the pathology of arterial and coronary vasospasm and may be a factor in myocardial ischemia and infarction. While this phenomenon is well documented, the underlying mechanism is unknown. The present study used isometric force measurements coupled with 45Ca2+ and Fura 2-AM techniques in aortic smooth muscle to probe transmembrane calcium movements and cytosolic calcium levels in an attempt to determine their relation to altered vasomotion in a rabbit model of dietary atherosclerosis. Following 10 weeks of cholesterol feeding (2%), basal (unstimulated) calcium influx was augmented 1.5-fold in atherosclerotic segments with no change in basal calcium efflux. Serotonin-stimulated calcium uptake was increased 1.9-fold in atherosclerotic segments and was accompanied by a fivefold increase in serotonin vasoconstrictor sensitivity and a 1.4-fold increase in serotonin-stimulated calcium efflux. Endothelial denudation did not alter either force generation or 45Ca2+ movements in serotonin-stimulated segments. In arterial smooth muscle cells dispersed from atherosclerotic vessels, basal and serotonin-stimulated cytosolic calcium levels were augmented approximately 2.3-fold and twofold, respectively. These findings contribute to our understanding of the cellular defects in calcium metabolism, which may ultimately explain the cellular basis of serotonin hypersensitivity in atherosclerotic arteries and certain arterial vasospastic syndromes in this disease state.
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PMID:Alterations in basal and serotonin-stimulated calcium permeability and vasoconstriction in atherosclerotic aorta. 794 12


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