Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteinuria is characteristic of many glomerular conditions, and often exceeds 2-3 g/24 h. There are several possible routes by which such profuse proteinuria might contribute to progression of the underlying pathology, whatever its type. First, proteinuria leads to a transit of protein through glomerular structures, including the glomerular capillary basement membrane, the mesangium and the epithelial cells, and to increased traffic of protein through the proximal tubules by pinocytosis of filtered protein. This traffic may be toxic to the cells concerned, and there is some evidence from 'overload' proteinuria induced in animals that this is so. Second, proteinuria leads to secondary hyperlipidemia with raised lipoproteins: mesangial cells have receptors for lipoproteins and in vitro, they are damaged by high concentrations, and there is evidence that hyperlipidemia leads to glomerulosclerosis. Third, proteinuria leads to hyperaggregability of platelets through alterations in plasma proteins, principally a fall in concentration of serum albumin and a rise in that of the von Willebrand factor, and possibly to increases in humoral coagulation cascades as well through losses of regulator proteins such as antithrombin III. There is evidence that anticoagulation and antiplatelet drugs will inhibit glomerulosclerosis in animals. Whether all or any of these mechanisms operate in human disease is not known; however, prognosis correlates well with duration and intensity of proteinuria in almost all proteinuric states and with the appearance and persistence of proteinuria in hematuric conditions. Therapies designed to reduce proteinuria per se may have a role in the treatment of glomerulopathies.
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PMID:Proteinuria and progression in human glomerular diseases. 225 80

Using a complex stimulating mixture containing ADP, epinephrine and collagen, a significantly (p less than 0.002) enhanced platelet aggregability, expressed as platelet sensitivity factor (PSF) was noted in platelet rich plasma of patients with proteinuria (PSF = 472 +/- 125), as against normal weight normolipidemic control subjects (PSF = 32.76 +/- 2.67). A significantly negative correlation (r. -0.579; p less than 0.001) was found between serum albumin concentration and the logarithmic values of platelet sensitivity factor. Plasma von Willebrand factor activity expressed as a percentage of normal was also significantly (p less than 0.001) higher in proteinuric patients (287% +/- 25.8) than in control subjects (99% +/- 5.02), but this hemostatic variable did not correlate with the logarithm of platelet sensitivity factor. Platelet aggregability was higher in hyperlipidemic nephrotic patients than in proteinuric patients with normal serum lipids, while renal failure led to a decrease of platelet function. The raised plasma levels of von Willebrand factor noted in proteinuric patients were not influenced by either hyperlipidemia or by chronic renal failure. It is concluded that changes affecting platelet function in the nephrotic syndrome are produced by other mechanisms than these leading to an increase of endothelia-derived von Willebrand factor. Both changes may, however, contribute to the thrombotic tendency of nephrotic patients.
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PMID:Plasma von Willebrand factor antigen and activity and platelet aggregability in patients with proteinuria. 261 81

Plasma lipids and haemostasis were investigated in 17 patients with hyperlipidaemia before and after 6 weeks supplementation with 6 g n-3 fatty acids. Nine of the patients had type IIa and 8 had type IV hyperlipidaemia. No effect on plasma cholesterol, LDL- or HDL-cholesterol were seen, but plasma triglycerides decreased after n-3 supplementation. Apolipoprotein B increased and apolipoprotein A1 decreased after the oil supplement. The bleeding time was prolonged, but platelet aggregation was unaltered by n-3 fatty acids. Protein C activity increased in type IIa and decreased in type IV after the supplement. Fibrinolysis was markedly depressed while von Willebrand factor antigen was reduced after intake of n-3 fatty acids.
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PMID:The effect of n-3 fatty acids on lipids and haemostasis in patients with type IIa and type IV hyperlipidaemia. 281 27

Platelet aggregability and plasma factor VIII-related antigen (F. VIIIR:AG) level in 16 ischemic heart disease (IHD) patients were increased by isometric exercise and these changes were prevented by administration of a lipid lowering agent, simfibrate, a derivative of clofibrate. Serum total cholesterol (TC) level decreased and the high density lipoprotein-cholesterol (HDL-C)/TC ratio increased with the treatment. Another 7 hyperlipidemics were administered with simfibrate. Platelet malondialdehyde (MDA) production decreased with improvement in lipid profile. In an in vitro study, platelet aggregability and the plasma level of von Willebrand factor (vWF) and F.VIIIR:AG of normal citrated blood were increased by passing it through a glass bead column. Combining above results of the three separate studies, it would be suggested that hyperlipidemia might enhance platelet activation in vivo, which occurred through contact of platelets to atherosclerotic rough vessel surface. The anti-platelet effect of simfibrate might be mediated through its effect on arachidonic pathway in platelets.
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PMID:Influence of lipids metabolism on platelet activation in vivo. 641 24

The relationship between antioxidants and endothelial cell injury was examined in 119 patients with (n = 48) or without (n = 71) vascular disease who were attending a hyperlipidaemia clinic. Serum levels of total antioxidant capacity, glutathione peroxidase (a protein antioxidant), von Willebrand factor (vWf, a specific endothelial cell product and marker of injury) and routine lipids were measured in the patients and from 58 healthy controls. Compared to controls, total antioxidant capacity (P < 0.01) and glutathione peroxidase (P < 0.0001) were lower whilst vWf was higher (P < 0.0001) amongst the patients. Comparing patients with and without vascular disease, glutathione peroxidase was lower (P < 0.03) and vWf was higher (P < 0.05) in the presence of vascular disease but there was no difference in levels of serum lipids or total antioxidant capacity. vWf and glutathione peroxidase were inversely correlated (r = -0.26, P < 0.005). We conclude that patients with hypercholesterolaemia have reduced antioxidant capacity and this is most severe in patients with clinically apparent vascular disease. This, linked to the finding of increased vWf in hypercholesterolaemia with highest levels in those patients with vascular disease, suggests that loss of antioxidant capacity may expose the vascular endothelium to excess oxidative damage. These results suggest a link between hypercholesterolaemia, impaired ability to resist free radical attack, and the development of atherosclerosis.
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PMID:Antioxidants, von Willebrand factor and endothelial cell injury in hypercholesterolaemia and vascular disease. 757 74

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

von Willebrand factor (vWf), risk factors for atherosclerosis, body mass index (BMI) and waist-to-hip ratio (WHR) were measured in 108 non-diabetic patients attending lipid and vascular disease clinics and in 107 normal asymptomatic controls. High levels of vWf and increased BMI relative to controls were found in patients with hyperlipidaemia and vascular disease, but WHR was higher only in patients with vascular disease. Total serum cholesterol concentration (P < 0.001), systolic blood pressure (P < 0.001), smoking (P < 0.02) and BMI (P < 0.001), but not WHR, were associated with vWf. As raised levels of vWf are a probable indicator of endothelial damage in vascular disease, these data suggest that obesity has an adverse influence on the endothelium and may help explain its link with cardiovascular disease.
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PMID:von Willebrand factor, the endothelium and obesity. 811 78

Vitamin A and its analogues have been reported to increase the release of tissue plasminogen activator in vitro. The aim of the present study was to reevaluate these findings and to investigate whether retinoids in doses used in dermatological therapy could enhance the release of endothelial fibrinolytic factors. Our results showed that endothelial cells incubated in vitro with retinoic acid increased the release of tissue plasminogen activator to the supernatant without concomitant secretion of plasminogen activator inhibitor-1. In patients treated with isotretinoin or etretinate these findings were confirmed, showing enhanced baseline tissue plasminogen activator concentrations in plasma in association with unchanged levels of plasminogen activator inhibitor-1 and von Willebrand factor. These findings are consistent with chronically augmented tissue plasminogen activator secretion without evidence of endothelial cell damage and may be of importance for the interpretation of the safety of lon-term therapy with regard to retinoid-induced hyperlipemia and the development of cardiovascular disease.
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PMID:Retinoids and fibrinolysis. 857 51

Our objective was to determine whether endothelial cell products von Willebrand factor and soluble E-selectin are related to serum lipids, lipoprotein (a), and vascular disease in patients with hyperlipidaemia. In order to achieve our aim, blood samples were obtained for four experiments from 1) 160 patients (49 with symptomatic vascular disease) with hypercholesterolaemia and an equal number of age and sex matched controls; 2) 31 patients who were studied serially before and after successful resolution of their hypercholesterolaemia; 3) 15 patients with hypertriglyceridaemia; and 4) 20 controls, half of whom consumed a lipid-rich breakfast. von Willebrand factor and soluble E-selectin were measured by enzyme linked immunosorbent assay (ELISA) using commercial reagents. In experiment (1) von Willebrand factor was increased in the patients with hypercholesterolaemia (P=0.0077) and was higher still in patients with vascular disease (P<0.0001). Soluble E-selectin was not influenced by hypercholesterolaemia or vascular disease. The correlation of von Willebrand factor with total and LDL cholesterol (both P<0.001) remained after both age and blood pressure were controlled. Experiment (2) showed that serial studies in patients over an average of 7 months a reduction in total cholesterol was associated with a reduction in von Willebrand factor (r=0.51, P=0.002). Experiment (3) demonstrated that von Willebrand factor was not increased in patients with hypertriglyceridaemia (median 8.9 mmol/L), and in experiment (4) a lipid-rich breakfast taken by fasted, healthy controls produced an increase in serum triglycerides (P<0.01) but did not influence von Willebrand factor over an 8 hour period. We conclude that von Willebrand factor, but not soluble E-selectin, is raised in hypercholesterolaemia and therefore may be a potential indicator of endothelial cell physiology in subjects with, or at risk of, atherosclerotic vascular disease.
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PMID:Von Willebrand factor and soluble E-selectin in hyperlipidaemia: relationship to lipids and vascular disease. 913 12

Modification of dietary fat composition may influence hemostatic variables, which are associated with increased risk of coronary heart disease (CHD). To address this question, we performed a controlled feeding study on 26 healthy male nonsmoking subjects with diets of differing fat composition. For the first 3 weeks, the subjects were given a diet calculated to supply 30% energy as total fat: 8% as monounsaturated, 4% as polyunsaturated, and 16% energy as saturated fatty acids, respectively (saturated diet). This was followed immediately by two diets taken in random order, each of 3-week duration and separated by an 8-week washout period on the subject's usual diet. Both diets were calculated to supply 30% of energy as fat: 14% monounsaturated, 6% as polyunsaturated, and 8% energy as saturated fatty acids. They both provided 5 g (approximately 1.7% energy) more of polyunsaturated fatty acids than the saturated fat diet; in one diet as long-chain n-3 fatty acids (n-3 diet) and in the other as linoleic acid (n-6 diet). Fasting plasma lipids, lipoproteins, and hemostatic factors were measured on the final 3 days of each dietary period. In a subset of 9 subjects the postprandial responses to a test meal were studied on the penultimate day of each period, each meal having the fat composition of its parent diet. On the n-3 diet compared with the n-6 diet, plasma triglyceride, HDL3 cholesterol, apoprotein AII, and fibrinogen concentrations were lower and HDL2 cholesterol concentration was higher (P = .0001, P = .003, P = .0001, P = .004, and P = .001, respectively). On both the n-3 and n-6 diets compared with the saturated diet, fasting plasma total and LDL cholesterol, apoprotein B, beta-thromboglobulin concentrations, and platelet counts were lower (P < .0001, P < .0001, P < .001, P < .01, and P < .05 respectively) and plasma Lp(a) and von Willebrand factor concentrations were higher (P = .02 and P < .01, respectively). Fasting factor VII coagulant activity (VIIc) was increased and apoprotein AI concentration reduced following the n-3 diet (P = .004 and P = .01, respectively) compared with the saturated diet. Plasma fibrinogen concentration was significantly greater following the n-6 diet than on the saturated diet (P = .02). Postprandially, plasma triglyceridemia was greater on the n-6 diet and lowest on the n-3 diet (P < .001) with the saturated diet being intermediate. Plasma VIIc was increased at 4 hours following the standardized test meals on the n-3 and n-6 diets (both P < .05) but not on the saturated diet. An increased intake of long chain n-3 fatty acids decreases fasting plasma triglyceride and apoprotein AII concentrations and increases HDL2 cholesterol concentrations and results in less postprandial lipemia but leads to an increase in VIIc. An increased intake of linoleic acid may raise plasma fibrinogen concentration. Decreasing the intake of saturated fatty acids reduces plasma LDL cholesterol and apoprotein B without affecting HDL cholesterol concentration independent of the type of polyunsaturated fatty acids in the diet. When advice is given to reduce saturated fat intake, it is important to ensure an appropriate ratio of n-3/n-6 fatty acids in the diet.
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PMID:Influence of n-6 versus n-3 polyunsaturated fatty acids in diets low in saturated fatty acids on plasma lipoproteins and hemostatic factors. 943 92


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