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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo effects of pantethine were investigated on serum lipids and platelet lipid and platelet functions in 31 diabetic patients with hyperlipidemia. Pantethine decreased cholesterol from 236 +/- 62 mg/dl (M +/- SD) to 217 +/- 51 mg/dl (p less than 0.01) and increased high density lipoprotein cholesterol from 40 +/- 11mg/dl to 43 +/- 15 mg/dl. The diabetic platelets were larger when accompanied by higher microviscosity that healthy platelets. The characteristics of lipid composition in diabetic platelets were high levels of free cholesterol, phospholipid, triglyceride, cholesterol ester, palmitoleic acid, linoleic acid and palmitoleic acid/palmitic acid and low levels of the molar ratio of free cholesterol/phospholipids, phosphatidylethanolamine, oleic acid, arachidonic acid and oleic acid/stearic acid. Pantethine normalized these values of fatty acids to the control levels, and concomitantly reduced significantly the hyperaggregation of platelets induced by 10(6) M ADP and the hyper-ADP release reaction from platelets when exposed to 2 microgram of collagen, and made the volume smaller and the microviscosity lower after oral administration. From these data, it was concluded that pantethine normalized the abnormalities of serum lipids as well as platelet lipid compositions and subsequently reduced the hyper-aggregation and hyper-release reactions through the changes of volume and microviscosity of the platelets in diabetes mellitus with hyperlipidemia.
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PMID:Influence of pantethine on platelet volume, microviscosity, lipid composition and functions in diabetes mellitus with hyperlipidemia. 725 94

This chapter focuses on the biochemical mechanisms that mediate glucose-stimulated insulin secretion (GSIS) from beta-cells of the islets of Langerhans and the potentiating role played by fatty acids. We summarize evidence supporting the idea that glucose metabolism is required for GSIS and that the GLUT-2 facilitated glucose transporter and the glucose phosphorylating enzyme glucokinase play important roles in measuring changes in extracellular glucose concentration. The idea that glucose metabolism is linked to insulin secretion through a sequence of events involving changes in ATP:ADP ratio, inhibition of ATP-sensitive K+ channels, and activation of voltage-gated Ca2+ channels is critically reviewed, and the relative importance of ATP generated from glycolytic versus mitochondrial metabolism is evaluated. We also present the growing concept that an important signal for insulin secretion may reside at the linkage between glucose and lipid metabolism, specifically the generation of the regulatory molecule malonyl CoA that promotes fatty acid esterification and inhibits oxidation. Finally, we show that in contrast to its short term potentiating effect on GSIS, long-term exposure of islets to high levels of fatty acids results in beta-cell dysfunction, suggesting that hyperlipidemia associated with obesity may play a causal role in the diminished GSIS characteristic of non insulin-dependent diabetes mellitus (NIDDM).
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PMID:Metabolic coupling factors in pancreatic beta-cell signal transduction. 757 98

The platelet function as well as parameters of lipid metabolism and glucose tolerance were investigated in 30 men with occlusive atherosclerotic arterial disease of the low extremities (IIIB or IV Fontaine's stage). The platelet aggregation, platelet survival, activity of intraplatelet metabolism of arachidonic acid, radiofibrinogen binding to platelet, circulating platelet aggregates and both the activity of factor VIII and the concentration of von Willebrand factor antigen in the plasma were measured. In the majority of patients the impairment of platelet aggregation with ADP, enhancement of radiofibrinogen binding to platelets and an increase of factor VIII level in the plasma were established. There was an interrelationship between platelet dysfunction and disturbances of lipid metabolism. Platelet survival was shortened in patients with moderate hyperlipidemia and correlated with a concentration of HDL-cholesterol in the serum. The radiofibrinogen binding to platelets was the most pronounced in patients with severe hyperlipidemia and correlated with a concentration of total cholesterol in the serum. The results may suggest the potential usefulness of antiplatelet drugs in patients with occlusive atherosclerotic arterial disease.
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PMID:[Function of platelets in patients with occlusive atherosclerotic arterial disease of the lower extremities]. 808 11

By the mediation of receptors in the endothelium, bradykinin, histamine, and thrombin--besides platelet-derived substances such as adenosine diphosphate and triphosphate (ADP, ATP) and serotonin--play an essential physiological role in the activation of the protective metabolic process in the endothelium, which is so important to vessel dilatation. The described process is attenuated by pathologic conditions such as e.g. hyperlipidaemia and hypertension. Furthermore, in the case of experimental hypertension, the production of contractile endothelial factors, which weaken the effect of the vasodilatory endothelial factors, is likely to increase. Obviously, an efficient antihypertensive therapy prevents from this endothelial dysfunction, at least in animal experiments.
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PMID:[Receptor-mediated endothelial vascular regulation (brief report)]. 818 16

To investigate the effects of the increased plasma lipid level on fibrinolysis, we measured the levels of fibrinolytic components in serially obtained plasma samples from healthy volunteers after the intake of different amounts of butter. Plasma triglyceride level increased significantly after butter intake compared to the control group. Eight hours after the intake of 100g of butter, plasminogen activator inhibitor 1 (PAI-1) level in plasma was significantly higher and euglobulin clot lysis time was significantly prolonged compared to those of the control group. There was no effect on plasma tissue plasminogen activator level. These results suggest that the temporary increase in plasma triglyceride level induced high PAI-1 level, resulting in impaired fibrinolytic activity. The effect of temporary hyperlipidemia on platelet function was also analyzed and revealed that the response of platelets to ADP and collagen was lower in the butter intake group compared to those of the control.
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PMID:Impaired fibrinolytic activity induced by ingestion of butter: effect of increased plasma lipids on the fibrinolytic activity. 832 87

Atherosclerosis is a progressive disease in which its clinical sequelae are manifest with increasing frequency as individual age. The present study seeks to better understand the mechanisms underlying this process by utilizing our previously-characterized rat model of early atherosclerosis induction to evaluate the effect of atherogenic plasma lipids on intracellular ionized calcium levels in rat platelets. Sprague-Dawley male rats were infused i.v. with 20% Lipofundin-S, a triglyceride-rich emulsion shown by us in previous studies to induce early athero-sclerosis and platelet hyperactivity. Twenty four hrs after the last infusion, blood was obtained by cardiac puncture. Washed platelets were loaded with aequorin, stimulated with ADP, and [Ca++]i was determined by measuring luminescence in platelets from lipid-infused vs. control rats. In platelets isolated from lipid-infused rats, [Ca++]i levels were 34% higher (p < or = 0.05) than in platelets from control animals. In addition, the mean, median, and mode diameters of platelets from lipid-treated rats were significantly greater (p < or = 0.001) than those of platelets from controls. With ADP as the aggregating agent, nifedipine at 1 microgram/ml caused a 27% (p < or = 0.05) inhibition of [Ca++]i release in platelets from lipid-treated rats, but showed no inhibitory action in platelets isolated from control animals. Hyperlipidemia results in elevated platelet [Ca++]i levels, with a concomitant increase in cell size, both indicating enhanced platelet function. Nifedipine modulates this increased activity in platelets isolated from lipid-infused rats, but not in cells from control animals.
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PMID:Intracellular ionized calcium ([Ca++]i) mobilization in platelets from rats receiving atherogenic lipids. Modulation by nifedipine. 886 50

In view of inducing action of hyperlipidemia on progression of nephropathy and relationships between thrombogenesis, atherogenesis and sclerosis, the authors examined fluvastatin effects on platelet-rheological hemostasis. The 12-week course in a dose 20-40 mg/ day produced minimal side effects while its hypolipidemic action was noticeable: a 18, 21 and 20% fall in concentrations of total cholesterol, LDL cholesterol, triglycerides, respectively. The platelet rheology underwent the following changes: spontaneous platelet aggregation went down from 2.58 +/- 0.3 to 1.64 +/- 0.27 r.units, ADP-induced platelet aggregation rose from 6.5 +/- 0.66 to 8.08 +/- 0.77 r.units. No marked changes were registered in hematocrit, plasma and blood density, red cell aggregation and deformability. Thus, active lowering of blood lipids was not associated with evident inhibition of platelet activity. The absence of this feedback in lipid-platelet relations probably indicates an independent significance of hemostatic disturbances in ischemic heart disease and needs further study.
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PMID:[The effect of a new hypolipemic preparation fluvastatin (Lescol) on rheological indices and hemostatic parameters]. 921 58

The present study was conducted to determine whether alimentary lipemia alters platelet activity in vivo. Normolipidemic volunteers were given a fatty meal and platelet function was assessed before, and 3 and 6 h after the meal. Platelet aggregability and secretion was determined using whole blood flow cytometry (expression of platelet P-selectin and fibrinogen binding), filtragometry ex vivo (reflecting platelet aggregability in vivo) and by measurements of platelet specific products in plasma (beta-thromboglobulin and platelet factor 4). Plasma triglycerides increased from 0.8 (0.6:1.1; median, 25th and 75th percentiles) to 1.7 (1.0:2.3) mmol/l at 3 h and returned to baseline after 6 h (P < 0.001, one-way ANOVA). Apo B-100 and apo B-48 were both markedly increased 3 h postprandially in the Sf 60-400 fraction (large VLDLs, P < 0.001 for both), whereas the Sf 20-60 (small VLDLs) and Sf 12-20 fractions (IDL) did not change. The platelet function assessments revealed that the percentage of platelets expressing P-selectin increased by 40% (5%; 64%) after 3 h and by 51% (- 7%; 85%) 6 h postprandially in unstimulated samples (P < 0.05 for both). In samples stimulated by ADP in vitro P-selectin expression increased by 45% (6%; 58%) after 3 h and by 30% (12%; 58%) (P<0.01 for both) after 6 h at 0.1 microM. Platelet P-selectin expression was less influenced at higher ADP concentrations. The plasma levels of beta-thromboglobulin (approximately 20 ng/ml) and platelet factor 4 (approximately 0.3 ng/ml) were not affected by the fat load. Flow cytometric analyses of fibrinogen binding and filtragometry measurements also failed to reveal any postprandial alterations. The present finding of enhanced platelet P-selectin expression suggests that platelets are mildly sensitized postprandially. Whether this is of importance for thrombus formation and atherosclerosis needs to be studied further.
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PMID:Alimentary lipemia enhances the membrane expression of platelet P-selectin without affecting other markers of platelet activation. 956 42

Platelet aggregation, induced by agonist-mediated activation of membrane glycoprotein (GP) IIb/IIIa, and binding of fibrinogen to GPIIb/IIIa, is commonly analyzed using an aggregometer in the clinical laboratories. However, this method has a limitation to get precise results on the samples with small number of platelet (less than 100,000/1) or hyperlipidemia. Recently, flow cytometry has been used to evaluate platelet function due to the detection of fibrinogen binding to activated platelets using fluorescence labeled fibrinogen or anti-fibrinogen antibody. However, the appropriate rule for evaluation of the results has not been established yet. We converted a ratio of fibrinogen binding platelets to a velocity per unit concentration of ADP as follows: a difference of two ratios of fibrinogen binding platelets on neighboring two ADP concentrations was divided by a difference of ADP concentrations. It was considered to be a mean velocity between the two ADP concentrations. We adopted the range of ADP concentration, which gave the maximum velocity, as an index of platelet activation. If the peak of maximum velocity move toward lower or higher ADP concentration, it means hyper- or hypoactivation of the platelets, respectively. The objectivity of this method may make it a useful technique for clinical examination of platelet function.
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PMID:[Measurement of fibrinogen binding to platelets by flow cytometry: evaluation method for reflecting platelet activation]. 969 71

To investigate the pathogenesis of hyperlipidemia-induced atherosclerosis, we examined age-dependent changes in platelet activity, blood coagulation and fibrinolysis in susceptibility to a high cholesterol diet (HCD) feeding in male ICR mice. Pretreatment of platelet-rich-plasma from HCD feeding mice for 3 days with epinephrine (300 microM) resulted in a marked enhancement of adenosine 5'-diphosphate (ADP: 0.1 microM) or collagen (0.7 microgram/ml)-stimulated aggregation compared with the same in control mice. Yohimbine as alpha 2-adrenergic blocker antagonized these aggregations in a dose-dependent manner. A significant increase in plasma total cholesterol and VLDL (very low-density lipoprotein)-LDL (low-density lipoprotein)-cholesterol and the liver/body weight ratio was observed in mice fed on HCD for 3 months (3-month HCD mice). In the early phase of this experiment, a significant increase in fibrinogen was observed. In the middle phase, increases in the activity of antithrombin III (ATIII) and alpha 2-plasmin inhibitor (alpha 2-Pl) followed. Plasminogen content gradually decreased in both normal diet and HCD mice throughout the experiment. The activity of plasminogen activator inhibitor (PAI) decreased in 3-month HCD mice. Morphological observation of the aortic arch from 3-month HCD mice revealed apparent atheromatous plaques not seen in control mice. These results suggest that 3-month HCD mice can be a convenient hyperlipidemia-induced atherosclerotic model and the changes in platelet activity, coagulation and fibrinolysis in the early phase may be a cause of pathologic changes in this model.
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PMID:Age-related changes in blood coagulation and fibrinolysis in mice fed on a high-cholesterol diet. 1006 66


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