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

The Ivanovas-Sieve (IVA-SIV) rat represents the only available animal model of endogenous hypertriglyceridemia, in the absence of obesity and/or overt diabetes. Since plasma lipids/lipoproteins can modulate platelet reactivity and eicosanoid metabolism, these were examined in two groups of Charles River (CR) and IVA-SIV rats of identical age. The IVA-SIV rats had 2-fold higher plasma triglycerides and a 55% higher number of circulating platelets; the number of platelets was significantly correlated with triglyceridemia. Platelet reactivity to ADP and to collagen was significantly reduced in these animals, whereas the formation of thromboxane B2 did not differ from that of the CR. After perfusion of platelet-rich plasma (PRP) through the aortas of animals of the two strains, platelet aggregability, already lower in the IVA-SIV, was reduced to a higher extent compared to the CR. Increased levels of the prostacyclin metabolite 6-keto-PGF1 alpha were identified in the perfusate from the aortas of IVA-SIV rats. Platelets from these animals also showed an increased sensitivity to Iloprost, a stable prostacyclin analogue, with an IC50 1.7-fold lower compared to CR rats. Spontaneous hypertriglyceridemia in the IVA-SIV model is not associated with platelet hyperresponsiveness, but rather with a reduced sensitivity to major aggregants.
Atherosclerosis 1988 Nov
PMID:Reduced platelet aggregability and increased vascular prostacyclin formation in a variant rat strain (IVA-SIV) with endogenous hypertriglyceridemia. 321 76

The effects of intake of dried garlic on blood coagulation, fibrinolysis, platelet aggregation, serum cholesterol levels, and blood pressure were studied in 20 patients with hyperlipoproteinemia over a period of four weeks. Fibrinogen and fibrinopeptide A significantly decreased by 10%. Streptokinase activated plasminogen and fibrinopeptide B beta 15-42 significantly increased by about 10%. Serum cholesterol levels significantly decreased by 10%. Systolic and diastolic blood pressure decreased. ADP and collagen induced platelet aggregation were not influenced.
Atherosclerosis 1988 Dec
PMID:Effect of dried garlic on blood coagulation, fibrinolysis, platelet aggregation and serum cholesterol levels in patients with hyperlipoproteinemia. 324 Mar 34

In a cross-sectional population study of 1132 unselected Eastern Finnish men aged 54 years, serum selenium concentration had a weak positive association with plasma HDL cholesterol (standardised partial regression coefficient, beta = 0.061, P = 0.019) and a fairly strong inverse relationship (beta = -0.223, P less than 0.001) with the extent of ADP-induced platelet aggregation. Neither plasma ascorbate concentration nor alpha-tocopherol to total cholesterol ratio had any association with plasma lipoproteins, platelet aggregability or prevalent ischaemic heart disease (IHD). When a covariance-correction was applied, men with ischaemic ECG findings at exercise had a lower mean serum selenium than others (81.5 micrograms/l vs. 85.9 micrograms/l, P less than 0.01 for difference). This difference was equally large for men with neither symptoms nor previous diagnosis of IHD.
Atherosclerosis 1988 Mar
PMID:Relationship of serum selenium and antioxidants to plasma lipoproteins, platelet aggregability and prevalent ischaemic heart disease in Eastern Finnish men. 325 19

Platelets play an essential role in the pathogenesis of atherosclerosis. Prostacyclin is a strong physiological inhibitor of platelets aggregation; prostacyclin indeed is involved in the regulation of platelet interactions with vessel walls and is considered to play a major role in the homeostatic balance. The impedance aggregometry allows the evaluation of platelet aggregation in whole blood. We valued platelet aggregation in whole blood induced by ADP (10 microM) in 40 healthy subjects and in 40 type II and type IV hyperlipemic subjects. Meanwhile by radioimmunoassay we dosed 6-keto PGF1 alpha, a stable product of prostacyclin, in 7 healthy subjects and in 33 hyperlipemic subjects. The statistical investigation put in evidence that at higher plasmatic levels of cholesterol, triglycerides and LDL correspond a greater platelet sensitivity to the aggregating agent, while the opposite happens to higher levels of HDL. The dosage of 6-keto PGF1 alpha put in evidence an increase of this substance in hyperlipemic as to healthy subjects, probably as an answer to augmented platelet aggregation.
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PMID:[Platelet aggregation in whole blood and prostacyclin in hyperlipemia types II and IV]. 337 26

The effect of giving diets containing 1.5 or 16% safflower or corn oil or 16% milk fat for 15 weeks on changes in the fatty acid composition of platelet phospholipids, in vitro platelet function, platelet survival and thrombosis was examined in rats. The mean plasma cholesterol concentration was not different among the groups. Diets containing 1.5% safflower or corn oil or 16% milk fat were associated with a decrease in 18:2n - 6 and an increase in 18:1n - 9 and the 20:4n - 6/18:2n - 6 ratio in the platelet phospholipids compared with the 16% safflower or corn oil diets. The 16% milk fat diet was associated with an increase in 14:0, 20:3n - 9, 22:3n - 9 and a decrease in 22:4n - 6 in platelet phospholipids compared with the other groups. There were no differences among the groups in the sensitivity of washed platelets to ADP-, thrombin- or collagen-induced aggregation, or thrombin- or collagen-induced release of granule contents or loss of arachidonate from platelet phospholipids. Platelet survival and turnover in rats given the diets were not different among the groups. In response to indwelling aortic catheters neither the percentage reduction in platelet survival nor the platelet accumulation on injured aortae and catheters were different among the groups. No macroscopic thrombi were seen in rats given any of the diets. The results of these studies provide no evidence that diet-induced alterations in fatty acid content (increases in 18:1n - 9, 20:3n - 9, 22:3n - 9, 20:3n - 6, and 20:4n - 6/18:2n - 6 ratio and a decrease in 22:4n - 6) of platelet phospholipids modify in vitro platelet function, platelet survival or turnover or influence thrombosis in rats.
Atherosclerosis 1987 Dec
PMID:Effect of the amount and type of dietary fat on platelet function, platelet survival and response to continuous aortic injury in rats. 342 55

The kinetics, in vivo distribution and sites of sequestration of autologous In-111-labelled platelets and other platelet function parameters were studied in ten patients with type IIa or IIb familial hypercholesterolaemia and thrombotic complications of atherosclerosis. The in vitro platelet aggregation response to ADP (P = 0.50) and collagen (P = 0.46); binding of fibrinogen to platelets (P = 0.61); and plasma beta-thromboglobulin levels (P = 0.42) of the patients and normal reference subjects did not differ significantly. The in vivo distribution of In-111-labelled platelets at equilibrium was within normal limits, and at the end of platelet life-span the sequestration pattern of labelled platelets in the reticuloendothelial system was also normal (spleen P = 0.31; liver P = 0.54). There was minimal evidence of in vivo platelet activation: only mean platelet lifespan (MPLS), 195 +/- 57 hours (difference between mean MPLS of patients and controls was 25 hours, with a 95% confidence interval from 23 to 31 hours; P = 0.02); mean platelet platelet turnover, 2298 +/- 824 platelets/microliter/hour (P = 0.005); plasma platelet factor 4 (P = 0.02); and the mean circulating platelet aggregate ratio, 0.8 +/- 0.1 (P = 0.02); differed significantly from normal. These results suggest that abnormalities of platelet function and kinetics observed in type II hyperlipoproteinaemia cannot be ascribed wholly to the hyperlipidaemia, but may be induced by the associated atherosclerosis.
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PMID:Kinetics and in vivo distribution of in-111-labelled platelets and platelet function in familial hypercholesterolaemia. 343 47

In this review, the major current problems related to the pharmacology and clinical use of antiplatelet drugs are discussed in relation to the physiopathology of the platelet-vessel wall interaction and arterial thrombus formation. Although platelet adhesion to injured vessels is a crucial step in thrombogenesis, none of the currently used antiaggregating drugs prevents this phenomenon. Why the normal endothelium does not react with platelets is not known. Thus we are unable to pharmacologically restore endothelial 'non-thrombogenicity' when lost by single or repeated injury. In contrast, more information is available on the mechanisms controlling and amplifying platelet activation by physiological stimuli (such as collagen and thrombin), and on their pharmacological modulation. The 3 main amplification loops involve arachidonic acid metabolism, ADP release and possibly the availability of a phospholipid platelet activating factor. These pathways are in turn activated by the phosphatidylinositol cycle. The most widely used antiaggregating drug is aspirin. It prevents the formation of arachidonic acid metabolites both in platelets and in vascular cells. The use of low-dose aspirin, thromboxane-synthase inhibitors, thromboxane receptor antagonists, epoprostenol (prostacyclin) and its stable analogues, and ticlopidine all appear to be promising pharmacological approaches, but none has so far been tested in clinical trials for thrombosis prevention. On the other hand, aspirin (in relatively large doses of 300 to 1500 mg daily), sulphinpyrazone and dipyridamole have been tested alone or in combination in the secondary prevention of thromboembolic complications. Aspirin has significantly reduced both the occurrence of myocardial infarction and mortality rate in patients with unstable angina and/or previous myocardial infarction; it has also proved beneficial in cerebrovascular disease. The beneficial effect of aspirin was dose-independent. In some of these trials aspirin was combined with either dipyridamole or sulphinpyrazone. When used alone, the latter compound has reduced sudden death or thromboembolic complications in patients with myocardial infarction. It remains to be established whether antiplatelet therapy may prevent or stop the progression of atherosclerosis.
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PMID:Current issues in thrombosis prevention with antiplatelet drugs. 352 85

An in vitro platelet aggregation assay has been used to characterize the platelet response of two inbred mouse strains, C57BL/6J and C3H/J. Arachidonic acid, ADP, ristocetin, and collagen, but not epinephrine, were effective inducers of platelet aggregation in C57BL/6 mice. In C3H mice, however, platelets responded differently to some, but not all, inducers of platelet aggregation. The difference between the two strains was particularly striking for arachidonic acid; at 0.375 microM arachidonic acid, platelets from C57BL/6 mice aggregated well, but platelets from C3H mice failed to aggregate. The two strains also differed in serotonin release from platelets. When the pool of platelet serotonin was labeled by incubating platelets with [14C]serotonin, the amount of label subsequently released from platelets in response to 0.375 microM arachidonic acid was 20.5% +/- 2.5 SE for C57BL/6 mice and 1.5% +/- 1.5 SE for C3H mice. The platelets from F1 progeny of a cross between C57BL/6 and C3H mice were indistinguishable in aggregation response from the C57BL/6 parent. The defect in aggregation response found in C3H mice appears to reside in the platelets rather than in the plasma. Experiments which involved adding the plasma of one strain to the washed platelets of the other strain indicated that C57BL/6 platelets aggregated well whether they were resuspended in plasma from C57BL/6 or C3H mice, while C3H platelets failed to aggregate regardless of the origin of the plasma. Strain C57BL/6 is susceptible to diet-induced formation of atherosclerotic lesions, but strain C3H is resistant to lesion formation. This genetic difference in atherosclerosis susceptibility is not related to the genetic difference in platelet aggregation since a recombinant inbred strain, BXH-9, is susceptible to atherosclerosis like the C57BL/6 parent but has the reduced platelet aggregation response of the C3H parent.
Atherosclerosis 1987 Apr
PMID:Characterization of a genetic difference in the platelet aggregation response of two inbred mouse strains, C57BL/6 and C3H/He. 360 15

Induction of hypercholesterolemia in rats by diets containing milk fat, cholesterol and taurocholate caused increased sensitivity of platelets to thrombin-induced aggregation and release, but not to ADP- or collagen-induced aggregation or release. This hypersensitivity to thrombin persisted in the presence of CP/CPK to convert released ADP to ATP, and aspirin to block formation of thromboxane A2. The increased sensitivity of platelets to thrombin in hypercholesterolemic animals was associated with an increase in 18:1 omega 9, 18:2 omega 6 and 20:3 omega 6 and a decrease in 20:4 omega 6 and 22:4 omega 6 in their phospholipids. Hypercholesterolemic animals also had a shortened platelet survival that did not appear to be due to an alteration in the lipid composition of the platelets. The diet-induced changes in platelet function were not associated with enhanced thrombosis in animals with indwelling aortic catheters, but were associated with increased platelet accumulation on the exposed subendothelium.
Atherosclerosis 1987 May
PMID:The effect of dietary saturated fat and cholesterol on platelet function, platelet survival and response to continuous aortic injury in rats. 360 33

The present study is the first work to evaluate thrombin-, ADP-, and collagen-induced platelet aggregation in laboratory rats receiving alimentation with the parenterally-administered lipid emulsion, Lipofundin-S, in doses sufficient to induce early atherosclerotic changes in the aorta. The aggregometry parameters of percent maximum aggregation, slope, and b2 or b20 almost uniformly indicate that such lipid treatments result in a statistically significant increased sensitivity of the platelets to ADP and collagen, while no change is noted with thrombin as the aggregating agent. By varying the amounts of ADP and collagen during aggregometry, we also demonstrate that the concentrations of these reagents necessary for equivalent platelet aggregation is substantially lower in lipid-infused rats than in controls. We conclude from this study that such lipid infusions can cause increased platelet aggregation, and that these lipids probably act in a synergistic fashion by affecting a variety of components which comprise the atherogenic process and its clinical endpoint. In addition, we believe that this experimental approach is of interest in that infusions of clinically-useful lipid emulsions are easily controlled, while alterations in platelet physiology and aortic structure occur concurrently and rapidly.
Atherosclerosis 1987 Jul
PMID:Platelet aggregability in rats with early atherosclerotic changes induced by parenterally-administered lipid emulsions. 363 50


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