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

The objective of this work was to characterize changes in platelet aggregability during postprandial hypertriglyceridemia with special emphasis on arachidonic acid metabolism. Ten healthy young men consumed 100 g fat after a fasting period of 12 hr. In-vitro platelet aggregation induced by ADP and collagen was measured at 0, 3, 5, and 9 hours after the fat intake. The major arachidonic acid metabolites, 12-hydroxyeicosatetraenoic acid (12-HETE), thromboxane A2 (TXA2), prostaglandin F2 alpha (PGF2a), and prostaglandin E2 (PGE2) produced during collagen-induced platelet activation were quantified by gas chromatography/mass spectrometry. A significant decrease in platelet aggregability induced by both ADP and collagen was detected during the postprandial hyperlipemia. No significant changes could be found in the prostanoid pattern of collagen activated platelets. There was no correlation between the degree of the inhibition of platelet aggregation and the relative or absolute increase of triglyceride-levels in the plasma during the postprandial hyperlipemia.
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PMID:Postprandial hyperlipemia inhibits platelet aggregation without affecting prostanoid metabolism. 130 85

Three main atherogenic processes are recognised today: hyperlipemia, arterial wall injury and parietal thrombosis. The role of hyperlipemia is supported, among other things, by the following: 1. Experimentally, protracted hyperlipemia can reproduce faithfully the lesions and all complications of advanced human atherosclerosis. 2. Immunohistochemically, plaque lipoproteins are identical with certain blood lipoproteins. 3. The incidence of atherosclerosis in different populations roughly parallels the average blood lipid levels of these populations. 4. Dietary and pharmacological reductions of blood lipid levels in certain populations have reduced the clinical manifestations of atherosclerosis in these populations. Prolonged hyperlipemia generates arterial plaques by causing penetration of blood lipids into the myocytes of the inner arterial wall, immigration of lipid-laden monocytes into the subendothelial space, and increased endothelial permeability for blood lipoproteins and mitogens. All types of arterial wall injury diminish the endothelial barrier and increase endothelial permeability for blood lipoproteins and mitogenic factors. Seven groups of naturally occurring arterial insults are recognised today: hemodynamic turbulence, hypertension, metabolic insults (including hyperlipemia), immune insults, viruses, exogenous chemicals, and obstruction of adventitial lymphatics. These insults usually cause a functional increase of endothelial permeability (when mild) or a loosening of interendothelial junctions (when intense). Parietal thrombosis develops practically only in atherosclerotic-almost never in normal-arteries. It is most frequently initiated by tiny breaks of plaque surfaces, breaks which expose blood to the highly thrombogenic collagen and lipid masses that abound in the atherosclerotic--but are absent from the normal arterial wall. parietal thrombi are overgrown by endothelium, turned into fibrous tissue and incorporated into the underlying plaques, whose thickness they can thus greatly increase.
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PMID:[New aspects on the etiology and pathogenesis of arteriosclerosis from the pathologic viewpoint]. 304 56

Current concepts of the pathogenesis of atherosclerosis have been reviewed, emphasizing some of the similarities of the mechanisms and events involved to those in inflammation. Figure 2 is a schematic summary of these events. Hyperlipidemia, or some component of hyperlipidemic serum, as well as other risk factors, are thought to cause endothelial injury, resulting in adhesion of platelets and/or monocytes and release of PDGF (and other growth factors), which leads to smooth muscle migration and proliferation. It is clear that endothelial injury need not be denuding, and in fact may consist of altered endothelial function (dysfunction); adhesion of monocytes, increased permeability of endothelium, and disturbances in growth control can occur without morphologically obvious endothelial injury. Hyperlipidemia, hypertension, smoking, immune injury, and other risk factors may contribute to this endothelial dysfunction in different ways and sometimes in combination. Smooth muscle cells produce large amounts of collagen, elastin, and proteoglycans and these form part of the atheromatous plaque. Hyperlipidemia contributes in a number of ways (as discussed earlier), and indeed, in the severely hypercholesterolemic patient, such as one with familial hypercholesterolemia, is alone sufficient to cause atherosclerosis in the absence of other risk factors. Foam cells of atheromatous plaques are derived both from macrophages and from smooth muscle cells; from macrophages via the beta-VLDL receptor and also possibly by way of LDL modification, recognized by the acetyl-LDL receptor (such as oxidized LDL); and from smooth muscle cells by less certain mechanisms. Extracellular lipid is derived from insudation from the lumen, particularly in the presence of hypercholesterolemia, and also from degenerating foam cells. Cholesterol accumulation in the plaque should be viewed as reflecting imbalance between influx and efflux, and it is possible that high-density lipoprotein is the molecule which helps clear the cholesterol from these accumulations (134). The diagram (right) also depicts the possibility that smooth muscle proliferation may occur without endothelial injury at all. There are several postulated mechanisms for such an occurrence: loss of growth control, direct smooth muscle injury (such as by LDL), and autonomous proliferation by the mechanisms suggested by Benditt. The theoretical scheme presented is based largely on in vitro work, only partly substantiated by experimental and human studies, and does not explain the precise mechanisms by which all risk factors increase the susceptibility to atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pathogenesis of atherosclerosis: atherogenesis and inflammation. 327 59

Blood coagulation and fibrinolysis in pregnancy with or without hyperlipidemia were studied. Blood samples were taken from 36 cases with early pregnancy, 59 cases with late pregnancy, and the relationship between the hemostatic changes and the concentrations of lipids was examined. The following results were obtained: 1. In early pregnancy, all cases were non-hyperlipidemic, but in 41% of late pregnancy cases, hyperlipidemia was found. 2. In late pregnancy without hyperlipidemia, shortening of prothrombin time and activated partial thromboplastin time, increases in platelet epinephrine, collagen aggregation, fibrinogen, and plasminogen, and a decrease in alpha 2-plasmin inhibitor were marked compared with those in early pregnancy without hyperlipidemia. 3. In late pregnancy with hyperlipidemia, the platelet count and fibrinogen were increased, and prothrombin and activated partial thromboplastin time were shortened compared with late pregnancy without hyperlipidemia. The platelet epinephrine aggregation was slightly decreased. Antithrombin III was increased and alpha 2-plasmin inhibitor was slightly decreased. 4. In the same subjects, the relationship between changes in blood coagulation and fibrinolysis in early and late pregnancies and total cholesterol was studied by the independent matched pair test. There were significant correlations (p less than 0.02, p less than 0.05) between activated partial thromboplastin time (r = -0.5998) and fibrinogen (r = 0.6230). From these results the author concluded that late pregnancy was a hypercoagulable state and this tendency was more obvious in late pregnancy with hyperlipidemia.
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PMID:[Hemostatic changes during pregnancy in reference to hyperlipidemia]. 339 35

Platelet aggregate ratios (PAR) were determined, and threshold concentrations (ED50) of epinephrine, adenosine diphosphate (ADP), and collagen were estimated by platelet aggregometry in 88 IDDM and 52 NIDDM patients without hyperlipidaemia or azotaemia, and in 106 healthy volunteers to revise the question of hyperaggregability in diabetes. ED50-s showed a tendency for negative correlation with age, significant in female but not in male controls. Similar trends were obtained in IDDM and NIDDM females, but were not in IDDM and NIDDM males. The ED50-s of different aggregating agents positively correlated with each other. ED50-s were higher in men than in women in both controls and IDDM patients. Similar but minor differences were observed between women and men in NIDDM. IDDM patients had significantly lower PAR and collagen ED50, and a tendency for epinephrine and ADP to be lower as compared to the sex- and age-matched controls. The differences of PAR were the same, while those of ED50-s were diminished in older NIDDM patients compared to the matched controls. It is concluded, that the previously observed general hyperaggregability in diabetic patients may have partly resulted from sex- and age differences. Threshold concentrations should be compared to sex- and age-matched controls.
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PMID:Sex- and age-dependence of platelet aggregation in diabetes mellitus. 341 60

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

Many human atherosclerotic lesions, showing no evidence of fissure or ulceration, contain a large amount of fibrin which may be in the form of mural thrombus on the intact surface of the plaque, in layers within the fibrous cap, in the lipid-rich centre, or diffusely distributed throughout the plaque. Small mural thrombi are invaded by SMCs and collagen is deposited in patterns closely resembling the early proliferative gelatinous lesions. In experimental animals, thrombi are converted into lesions with all the characteristics of fibrous plaques, and in saphenous-vein bypass grafts, fibrin deposition is the main cause of wall thickening and occlusion. There seems little doubt that fibrin deposition can both initiate atherogenesis and contribute to the growth of plaques. Epidemiological studies indicate that increased levels of fibrinogen and clotting activity are associated with accelerated atherosclerosis, and although blood fibrinolytic activity has given inconsistent results, in arterial intima both fibrinolytic activity and plasminogen concentration are decreased in cardiovascular disease. Fibrin may stimulate cell proliferation by providing a scaffold along which cells migrate, and by binding fibronectin, which stimulates cell migration and adhesion. Fibrin degradation products, which are present in the intima, may stimulate mitogenesis and collagen synthesis, attract leukocytes, and alter endothelial permeability and vascular tone. In the advanced plaque fibrin may be involved in the tight binding of LDL and accumulation of lipid. Thus there is extensive evidence that enhanced blood coagulation is a risk factor not only for thrombotic occlusion, but also for atherogenesis. Enhanced blood coagulation frequently coexists with hyperlipidaemia and, together, these may have a synergistic effect on atherogenesis.
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PMID:Fibrinogen, fibrin and fibrin degradation products in relation to atherosclerosis. 352 31

Studies of experimental atherosclerosis in the dog demonstrate that many months at plasma cholesterol concentrations greater than 750 mg/dl are required to produce lipid containing atherosclerotic lesions. Since it has been recognized for many years that vascular injury in combination with hyperlipemia will result in rapid formation of atherosclerotic lesions, we attempted to combine vascular injury with hyperlipemia as a means of accelerating this process in the dog. Injury was produced in pulmonary arteries with experimental Dirofilaria immitis (DI or heartworm) infection. This filarial parasite produces characteristic lipid-free lesions containing smooth muscle cells and occasional monocytes and collagen. Plasma cholesterol was increased by feeding 10 dogs an essential fatty acid-deficient diet (EFAD) for 90 days. Five of the EFAD dogs were infected with 30 to 31 adult DI worms to produce pulmonary artery injury. The remaining 5 EFAD dogs were not subjected to any form of vascular injury. An additional 5 control dogs were not subjected to vascular injury nor to the EFAD diet. The arteries of dogs infected with DI developed myointimal proliferative lesions which contained smooth muscle cells and macrophages. In addition, the EFAD diet produced significant elevations in LDL but not VLDL plasma cholesterol in all 10 dogs fed the diet. However, the plasma cholesterol was less than 750 mg/dl in all EFAD-fed dogs. Although smooth muscle cells and macrophages in the pulmonary arteries of DI-infected dogs were focal points for lipid accumulation, cholesterol content of these injured arteries was not increased compared to noninjured EFAD dogs. The results suggest that even severe vascular injury does not reduce the threshold of 750 mg/dl required to produce significant lipid accumulation in canine arteries.
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PMID:A study of atherosclerotic lesion development in the injured pulmonary arteries of dogs with induced hyperlipemia. 357 20

A 68-year-old man with apparently light-exacerbated erythematous cutaneous plaques on his face and on the dorsa of his hands was found to have late-onset erythropoietic protoporphyria, diabetes mellitus, and hyperlipidemia. Extensive deposits of material that stained with periodic acid-Schiff were present in the lesional dermis. Monospecific antibody studies showed this material to be mainly type IV collagen. These findings strongly suggest that the lesions are a manifestation of erythropoietic protoporphyria. The late onset and asymptomatic unusual cutaneous lesions appear to be a new presentation of the disease.
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PMID:Late-onset erythropoietic protoporphyria with unusual cutaneous features. 403 26

Ther are several main mechanisms that allow us to understand a number of the hepatic and metabolic effects of ethanol. Ethanol is oxidized in the liver to two products (hydrogen and acetaldehyde), to which many of the effects of ethanol can be attributed. The hydrogen generated alters the redox state, and though this effect is attenuated after chronic ethanol consumption, it may still be sufficient to explain alterations in lipid metabolism, possibly increased collagen deposition, and, under special circumstances, depression of protein synthesis. Acetaldehyde impairs microtubules, decreases protein secretion, and causes protein retention and ballooning of the hepatocyte. Acetaldehyde exerts toxicity also with regard to other key cellular functions, particularly in the mitochondria, and it may promote peroxidation of the cellular membranes. It is noteworthy that after chronic consumption of ethanol, there is increased acetaldehyde, in part because of decreased disposition in the mitochondria and partly because of induction of an alternative pathway of ethanol metabolism, namely the microsomal ethanol-oxidizing system. Indeed, this MEOS increases in activity after chronic ethanol consumption, with cross induction and acceleration of the metabolism of other drugs and increased lipoprotein production with hyperlipemia. There is also increased microsomal activation of hepatotoxic compounds (including drugs and possibly vitamin A). Fibrosis and cirrhosis can develop despite an associated adequate diet and even in the absence of alcoholic hepatitis. They are preceded by myofibroblasts and fibroblast proliferation. What eventually causes the increased number of myofibroblasts and promotes fibrosis is unclear, nor do we know the relative role of hepatocytes or mesenchymal cells in the process of fibroplasis. Possibly selective roles in this process of specific nutritional factors remain to be elucidated.
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PMID:Alcohol, protein nutrition, and liver injury. 634 74


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