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)

An increased platelet-vessel wall interaction plays an important role in most forms of cardiovascular disease. In healthy arteries, the vascular endothelium prevents platelet adhesion and aggregation. As a mediator of this protective function, the endothelium produces prostacyclin, endothelium-derived nitric oxide and tissue plasminogen activator. Cardiovascular risk factors such as hypertension, hyperlipidemia and diabetes are associated with an increased platelet activation and with decreased antithrombotic properties of the blood vessel wall. The available inhibitors of platelet function interfere only with one of various mechanisms of platelet activation and of the platelet-vessel wall interaction. Prostaglandin inhibitors, such as aspirin and newer, more specific inhibitors, prevent the production and/or the effect of thromboxane A2 on platelets and the blood vessel wall. Other drugs interfere with the effect of adenosine diphosphate on platelets, or they increase intracellular concentration of cyclic GMP or AMP in platelets and vascular smooth muscle cells. The protective effects of platelet inhibitors in primary and particularly in secondary prevention of cardiovascular diseases have been documented in numerous studies. The successful clinical use of these substances, however, requires a selective prescription of the drugs in patients with cardiovascular disease.
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PMID:[Thrombocyte inhibitors in cardiovascular therapy]. 221 49

The vascular endothelium, in response to pulsatile flow and vasoactive agents including acetylcholine, secretes the endothelium-derived relaxing factor (EDRF), a substance which regulates vascular tone. Recent interest in EDRF has focused on its possible dysfunction in atherosclerosis. In animal models of the disease, endothelium-dependent relaxation is markedly reduced. The continuous exposure of the endothelium in hyperlipidaemia to high concentrations of low-density lipoprotein (LDL), a known atherogenic risk factor, may explain this dysfunction. Here, we demonstrate that pathophysiological concentrations of LDL directly inhibit endothelium-dependent relaxation. Chemically modified LDL, in contrast, is inactive, implying that the inhibition is through a receptor-dependent mechanism.
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PMID:Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta. 310 33

This article reviews the experimental and clinical evidence regarding heparin therapy in the prophylaxis of coronary heart disease. The actions of heparin take place at the vascular endothelium where injected heparin concentrates, and within the bloodstream. At the endothelium heparin acts to prevent endothelial injury, prevent thrombin generation, prevent platelet adhesion to endothelium, and to decrease uptake of serum lipoproteins. Within the bloodstream heparin increases lipoprotein lipase activity and reduces the concentration of atherogenic very low-density lipoproteins. The reduction in lipemia enhances oxygen transfer from blood to the tissues, and decreases thrombin or ADP-induced platelet aggregation. Heparin increases the concentration of high-density lipoproteins. It decreases hypercoagulability and inhibits overactivation of serum complement. Heparin reduced atherosclerosis in most studies in cholesterol-fed animals. In human subjects who had a myocardial infarct at least one year before the onset of treatment, long-term intermittent heparin therapy significantly decreased cardiovascular deaths as compared to control groups.
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PMID:Heparin and atherosclerosis. A review of old and recent findings. 698 41

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

Oversulfated fucoidan fragments (20-40 and 40-60 kDa) were prepared, and their fibrinolytic and anticoagulant activities were compared with those of oversulfated fucoidan (100-130 kDa) reported previously [Soeda et al., Biochem. Pharmacol. 43, 1853-1858, 1992]. The results of these experiments indicated that the in vitro abilities of oversulfated fucoidan to stimulate tissue plasminogen activator (t-PA)-catalyzed plasminogen activation and to potentiate thrombin inhibition by antithrombin III or heparin cofactor II decreased with a decrease in its molecular size. However, the preventive effects of both fucoidan fragments on endotoxin-induced hepatic vein thrombosis in hyperlipemic rats were almost the same as that of oversulfated fucoidan (100-130 kDa). We also found that, unlike heparin treatment, the concentrations of serum and vascular endothelium t-PA in rats treated with oversulfated fucoidan or its fragments (1 mg each/kg/week) were maintained at normal levels. The 20-40 and 40-60 kDa fragments had an ability to decrease the elevated levels of serum cholesterol in hyperlipemic rats, whereas the 100-130 kDa fucoidan derivative did not. These results suggest that oversulfated fucoidan and its fragments have another function(s), besides the regulation of blood coagulation and fibrinolysis, and are of therapeutic benefit for the prevention of thrombus formation in hyperlipemia.
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PMID:Preparation of oversulfated fucoidan fragments and evaluation of their antithrombotic activities. 830 63

Catabolism of triglyceride-rich lipoproteins, including chylomicrons (CM), is reduced in the nephrotic syndrome. It has been suggested that hyperlipidemia per se might lead to reduced CM catabolism by saturating catabolic sites. Evidence also implicates disordered high-density lipoprotein function as reducing the activity of lipoprotein lipase (LPL), the final effector of CM lipolysis. To establish whether CM lipolysis would be abnormal in the absence of either abnormal rat lipoproteins or hyperlipidemia, we measured CM lipolysis by isolated perfused hearts of rats with passive Heymann nephritis. We found that lipolysis was significantly reduced by 30% at 30 minutes (246 +/- 40 mumol v 164 +/- 10 mumol fatty acid released/hr, P < 0.05). Uptake of fatty acids was also significantly less in nephrotic hearts than in control hearts (7.25% +/- 0.93% of dose v 3.32% +/- 0.011% of dose, P < 0.01). Total heart LPL activity was reduced by 40% in hearts of nephrotic animals (368.5 +/- 39.4 mumol v 210.6 +/- 25.9 mumol free fatty acid released/hr/g heart, P < 0.01). The heparin-releasable LPL pool is that pool bound to the vascular endothelium and represents the biologically active fraction. We perfused hearts with heparin and found that heparin-releasable LPL was reduced by an order of magnitude in hearts from nephrotic rats (173 +/- 33 mumol v 19.4 +/- 11.7 mumol free fatty acid released/hr/heart, P < 0.001). The decrease in this pool represented nearly entirely the difference in total heart LPL in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defective lipolysis persists in hearts of rats with heymann nephritis in the absence of nephrotic plasma. 832 75

Mononuclear cells, isolated from the blood of hyperlipidaemic patients, are hyper-reactive and possess an increased propensity to adhere to vascular endothelial cells. Hyperlipidaemia is also associated with a dysfunctional endothelium, to which mononuclear cells stick with greater avidity. In order to assess the importance of lipid peroxidation and free-radical generation in these processes, we have investigated the effects of probucol on mononuclear cell adhesion to vascular endothelial cells in vivo and in vitro in the cholesterol-fed rabbit. New Zealand White rabbits were fed either: (i) control chow (n = 15), (ii) 2% cholesterol (n = 11), or (iii) 2% cholesterol with 1% probucol (n = 11). Mononuclear cell adherence to endothelium in the common carotid artery was assessed 5 weeks after the start of the experimental diet using the Hoechst 33342 staining technique. The 2% cholesterol diet caused a more than 6-fold increase in mean mononuclear cell adherence (P < 0.001). Concurrent probucol therapy abrogated the effects of cholesterol feeding, and in animals in this group, in vivo mononuclear cell adherence did not differ significantly from control animals. In vivo mononuclear cell adherence was directly related to serum cholesterol levels (r = 0.68, P < 0.0001) and inversely related to serum probucol concentrations (r = -0.63, P < 0.002). Concurrent probucol therapy also reduced the in vitro binding of mononuclear cells, isolated from hypercholesterolaemic animals, to endothelial cell monolayers (P < 0.01). These data suggest that the increased binding of mononuclear cells to vascular endothelium of cholesterol-fed rabbits may be a free radical mediated process that is inhibited by antioxidants.
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PMID:Probucol inhibits mononuclear cell adhesion to vascular endothelium in the cholesterol-fed rabbit. 835 49

Hyperlipidemia following successful renal transplantation is a frequent and persistent disorder, and lipid abnormalities are associated with ischemic heart disease. Correlates have been found to cyclosporine and steroids as the major causes of lipid disorders. Cardiovascular disease is currently the major cause of death among renal graft recipients in the long run. Therefore, lipid lowering therapy appears to be useful in those patients without cardiovascular disease (primary prevention) and is mandatory in those with established coronary artery disease (secondary prevention). Because of the multiplicity of other cardiovascular risk factors, hyperlipidemia might only be of minor importance. On the other hand, lipids may even accelerate the development of arteriosclerosis in a preinjured vascular endothelium. Dietary modification or reduction of dietary fat is considered to be the first line of antilipemic therapy. Unfortunately, hyperlipidemia appears not to be responsive to modification of dietary fat without weight reduction. In general, patients taking immunosuppressive drugs after organ transplantation are grouped under high risk population when pharmacological intervention is selected, since only some lipid lowering drugs are safe and efficacious in short-term studies and when used with precaution. Low-dose HMG-CoA reductase inhibitor is the drug of choice for lowering LDL cholesterol. Immunosuppression withdrawal protocols have successfully been used to control massive hyperlipidemia in immunologically stable patients in the long term. Although evidence from prospective controlled intervention studies is lacking, it is reasonable to adopt the principle of a broad-based approach aimed at reducing LDL cholesterol as well as other major risk factors for cardiovascular disease in this patient population. The likelihood is that effective control of serum lipids and lipoproteins may achieve a similar beneficial reduction in absolute mortality in renal transplant recipients as already demonstrated in individuals without kidney disease but with cardiovascular damage.
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PMID:Clinical utility of antilipidemic therapies in chronic renal allograft failure. 858 86

Cardiovascular diseases remain to be the 4th rank of top ten causes of mortality in Taiwan in recent years. Atherosclerosis and coronary artery disease, which often culminating in the occurrence of myocardial infarction and congestive heart failure, are responsible for the majority of these death. One of the prominent features of atherosclerotic lesion is local accumulation of lipids, mainly in the forms of cholesteryl ester and free cholesterol, either within cells or extracellularly in matrix. Repeated endothelial injury and enhanced lipid infiltration are critical events in the development of atherosclerosis. Plasma lipoproteins may enter the arterial wall through endothelium, either transcellularly via vesicular transport or paracellularly via intercellular junction. Our previous studies have demonstrated that most of the arterial endothelial cells in mitosis are associated with the leakage of fluorescently labeled albumin and low density lipoproteins. Subsequently, such transendothelial leakage of macromolecules is also shown to be associated with endothelial cell death as assessed by immunocytochemical staining for IgG. These findings suggested that transiently leaky junctions occurring during endothelial cell turnover may provide potentially important pathways for increasing transport or leakage of macromolecules, including atherogenic LDL, across the vascular endothelium. Electron microscopic study using horseradish peroxidase as a tracer revealed markedly widening of intercellular junctions around endothelial cells in mitosis providing direct evidence in support of "cell turnover-leaky junction" theory for the localization of atherogenesis. Hypertension, smoking, diabetes, and hyperlipidemia are well-known major risk factors for atherosclerosis and coronary heart disease. In a series of investigations, we examined the hypothesis that hypertension smoking, diabetes, and hyperlipidemia increase the arterial endothelial cell turnover and hence transendothelial macromolecular transport, which may have some implications in increasing lipid entry and thus, accelerating atherogenesis. Animal experiments were performed in adult male spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) normotensive rats, and Sprague-Dawley (SD) rats. SHRs were used as hypertensive group with WKY rats as normotensive control. SD rats were given nicotine at a dose of 5 mg/Kg body wt/ day in their drinking water to mimic smoking effect over a period of 6 weeks. Diabetes was induced in SD rats by single intraperitoneal injection of 60 mg/Kg body wt of streptozotocin. The duration of diabetes was 6 weeks. Also, SD rats were fed a diet containing 5% cholesterol for 6 weeks to induce hyperlipidemia. Age-matched rats of comparable number served as control for each experimental group. In en face preparations of thoracic aorta, mitotic endothelial cells were identified by hematoxylin staining, immunoglobulin G-containing dying or dead endothelial cells were detected by an indirect immunoperoxidase method, and endothelial leakage to Evans blue-albumin (EBA) complexes (5 minutes after intravenous injection) was visualized and quantified by fluorescence microscopy. The results showed that SHR, chronic oral nicotine-treated rats, diabetic, rats, and hyperlipidemic rats, when compared to control rats, had higher values for the frequency of endothelial cell death and the number density of EBA leaky foci in the aorta. These findings suggested that hypertension, cigarette smoking, diabetes mellitus, and hyperlipidemia become risk factors in atherogenesis by increasing the rate of arterial endothelial cell turnover and the associated endothelial cell turnover and the to the consequent enhanced entry of atherogenic lipoproteins into the arterial wall and accelerated atherogenesis.
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PMID:Risk factors, endothelial cell turnover and lipid transport in atherogenesis. 903 45

Most of the indications for cardiovascular operation and many of its complications are in large part due to advanced atherosclerosis. The pathogenesis of atherosclerosis involves inflammatory infiltration of the vessel wall, cellular proliferation, fibrous plaque formation, and ultimately plaque rupture and occlusive thrombosis. Many of these events are linked, at least initially, to chronic injury of the vascular endothelium. Endothelial cell injury from hypertension, diabetes mellitus, hyperlipidemia, fluctuating shear stress, smoking, or transplant rejection disrupts normal endothelial cell function. This results in the loss of the constitutive protective mechanisms and an increase in inflammatory, procoagulant, vasoactive, and fibroproliferative responses to injury. These changes promote vasospasm, intimal proliferation, and thrombus formation, all of which play a significant role in the initiation, progression, and clinical manifestations of atherosclerosis. Understanding the role of the chronically injured endothelium and its interactions with circulating immune cells and the underlying smooth muscle cells may lead to novel therapeutic interventions for the prevention and treatment of atherosclerosis.
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PMID:Endothelial cell injury in cardiovascular surgery: atherosclerosis. 906 32


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