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

Two key events in the atherogenic cascade are the focal influx and accumulation of low-density lipoprotein (LDL) cholesterol at arterial sites having a predilection for atherosclerotic lesion development and the recruitment of blood monocytes to these lesion-prone sites. Both processes are enhanced in the setting of hyperlipidemia and dyslipoproteinemia. The monocytes recruited to the endothelial surface subsequently migrate to the subendothelial space under the directed guidance of chemoattractants, such as monocyte chemotactic protein-1 and oxidatively modified LDL. These cells then undergo activation-differentiation to become macrophages. At the same time, LDL, and probably other lipoproteins such as the small dense LDL particles and lipoprotein (a), traverse the endothelium and undergo oxidative modification by reactive oxygen species. These oxidatively modified lipoproteins are recognizable by the non-down-regulating macrophage scavenger receptor. Their uptake by these receptors results in the formation of the foam cell characteristic of early-stage atherosclerosis. As monocyte recruitment and lipoprotein influx continue, the lesion grows and develops into the fatty streak. Subsequent foam cell necrosis due to the influence of cytotoxic oxidatively modified LDL and increased collagen synthesis by intimal smooth muscle cells lead to the established atherosclerotic lesion referred to as the fibrous plaque. As our understanding of the mechanisms involved in the pathogenesis of atherosclerosis has evolved over the past few years, novel strategies for intervention in the atherogenic process have emerged.
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PMID:A modern view of atherogenesis. 843 61

Cardiovascular disease remains the major cause of death for postmenopausal women in Western societies. The majority of epidemiological studies indicate that postmenopausal oestrogen replacement therapy is associated with a 50% reduction in the risk of cardiovascular disease, with much of the reduction being mediated by changes in the plasma concentration of cholesterol within high and low density lipoproteins. In addition to favourably influencing the plasma concentration of lipoproteins, oestrogens also influence the complex metabolism of lipoproteins in the arterial wall, helping to impede the formation of the atherosclerotic plaque. Whilst oestrogens alter endothelial function, vascular reactivity and fibrinolysis, these changes are also seen with reduction of LDL cholesterol and may partly reflect the altered concentration of plasma lipoproteins induced by oestrogens. Oral oestrogens have substantially greater favourable effects on LDL and HDL cholesterol than their transdermal counterparts but also result in greater hypertriglyceridaemia. Most progestogens antagonize the beneficial effects of oestrogens on lipoproteins in a dose-dependent manner; however, cyclical use of low doses of progestogens with an oral oestrogen generally retains a net beneficial effect. Lipoprotein levels fluctuate during cyclical therapy, the most adverse changes being noted at the end of the progestogen phase. Lipoprotein concentrations are constant during continuous combined regimens which have the potential for more prolonged exposure to an adverse progestational effect. Despite adverse effects on the lipoprotein profile, animal studies suggest that progestogens do not substantially reverse the beneficial effects of oestrogens on the development of atherosclerosis. Finally, oestrogen therapy may be useful in the management of postmenopausal women with hyperlipidaemia, and also in the secondary prevention of clinical sequelae in women with established atherosclerosis.
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PMID:Oestrogens and atherosclerotic vascular disease--lipid factors. 843 58

Uncontrolled oxidation has been implicated in the pathogenesis of atherosclerosis. In order to investigate the possible influence of hyperlipidemia on endogenous antioxidant status, the effects of dietary cholesterol supplementation on antioxidant enzymes and in vitro susceptibility to oxidative challenge (as measured by glutathione depletion and lipid peroxidation) were compared in two species exhibiting high and low susceptibilities to atherosclerosis, namely Japanese quail and rat, respectively. Standard diets were supplemented with cholesterol and cholic acid (1.0 and 0.5%, by weight, respectively) and assessments of antioxidant status made in red cells, liver, kidney and heart after 1, 2, 5 and 8 weeks. In contrast to the absence of detectable antioxidant alterations in rats, quail showed complex tissue-dependent changes, including increases (possibly adaptive) in antioxidant enzyme activities (usually first apparent at 2 weeks), enhanced susceptibility to peroxide-induced glutathione depletion (heart, kidney and liver) at 5 weeks and decreased sensitivity to lipid oxidation (heart and liver) at 8 weeks. Our results indicate an association of hyperlipidemia with complex time-dependent alterations in antioxidant components in an atherosclerosis-susceptible species prior to the appearance of visible atherosclerotic lesions. Future studies will focus on alterations in antioxidant components associated with atherosclerotic plaque development.
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PMID:Effects of hypercholesterolemia on tissue antioxidant status in two species differing in susceptibility to atherosclerosis. 845 40

We investigated the mechanisms by which corticosteroids affect atherosclerosis. Male New Zealand White rabbits were injected with 0.125 mg dexamethasone (n = 10) or vehicle (control group, n = 10). Both groups were fed a 1% cholesterol diet for 8 weeks. Although the dexamethasone-treated animals exhibited a greater degree of hyperlipidemia, they exhibited significantly less atherosclerotic plaque of the aortic surface than control animals (7.8% versus 47.2%). Immunofluorescence study of the aortic plaque specimens showed that dexamethasone administration reduced both macrophages and T lymphocytes. In vitro, dexamethasone suppressed the proliferation and differentiation of U937 cells and inhibited uptake and degradation of beta-very low density lipoproteins by mouse peritoneal macrophages. These findings suggest that dexamethasone suppresses the development of atherosclerosis in the aorta of rabbits by inhibiting recruitment and proliferation of macrophages and the formation of foam cells in plaques.
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PMID:Dexamethasone-induced suppression of aortic atherosclerosis in cholesterol-fed rabbits. Possible mechanisms. 849 10

The coronary atherosclerotic plaque progresses in successive stages, determined by phenomena such as spasm, thrombosis and inflammation. Studies of regression are hindered by methodological problems involving the variability of angiographic results over intervals of several years. Longitudinal clinical studies are probably more useful. For long-term clinical outcome, it appears that stabilisation of young plaques is more important than regression of older plaques. To this end, cessation of smoking seems the most effective means; progressive plaques are most often seen early in the disease, in patients under 60 years of age, of whom more than 70% are smokers. The inevitable lack of studies as rigorous as those dealing with hyperlipidaemia reduction should not be used as a pretext for scruples leading to ignoring the results of clinical practice. Prevention by diet is no doubt essential, but prospective studies are still rare and biases are numerous. The same is true for physical exercise.
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PMID:[Secondary prevention of atherosclerosis: effects on coronary plaques and on myocardial ischemia]. 857 Oct 44

Numerous studies have shown that patients with peripheral and carotid atherosclerosis have a high prevalence of hyperlipidemia, and clinical trials using either angiography or ultrasonography have now demonstrated regression of both femoral and carotid arterial plaque during lipid-lowering therapy. However, whether patients with peripheral and carotid atherosclerosis receive adequate attention to lipid risk factors has not been studied. To evaluate physician recognition and management of hypercholesterolemia in these two patient populations, we reviewed the charts of 80 consecutive patients undergoing revascularization for symptomatic peripheral and carotid occlusive disease at a university medical center between 1990 and 1993. Physician practices were assessed for each patient by noting whether hypercholesterolemia was (1) screened for during the hospitalization and, if present, (2) documented as a problem, (3) managed in-hospital, or (4) given appropriate intervention at discharge. While 73% of patients received some type of lipid case-finding perioperatively, less than one quarter of these were assessed for hyperlipidemia by the physician during the initial history. Moreover, of the 66% of screened patients found to be hypercholesterolemic, only 16% had documentation of the problem, only 24% received in-hospital management, and only 13% received intervention at discharge. These findings suggest that patients with documented peripheral and carotid atherosclerotic vascular disease probably receive inadequate attention to lipid risk factors and indicate the need for greater awareness and management of lipid disorders in these two patient populations by all involved physicians.
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PMID:Physician recognition of hypercholesterolemia in patients undergoing peripheral and carotid artery revascularization. 857 65

The characteristics of a subset of atherosclerotic plaques that is responsible for myocardial infarction (infarctogenic plaques) are increasingly well defined. They include moderate size, a thin fibrous cap, and a large lipid pool. Fissuring of the cap leads to thrombotic occlusion and often to an acute coronary event. Physical stresses on, and proteolytic weakening of, the cap--both related to effects of hyperlipidemia on the plaque--increase the risk of fissuring. Treatment of hyperlipidemia leads to regression of experimental atherosclerosis, promotes regression and reduces progression of human coronary artery disease. The arterial changes in humans are predictive of reduced incidence of coronary events. This sequence of events may reflect gradual depletion of plaque lipids, and also a more rapid depletion of chronic inflammatory cells in the plaque cap that are the source of collagenase and other proteases. The primary objective of lipid-lowering therapy appears to be the induction of these changes in infarctogenic plaques, and vigorous treatment should be targeted on patients likely to harbor such plaques.
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PMID:Coronary heart disease prevention and the infarctogenic plaque. 868 41

Although it has been known for over 50 years that lipoprotein lipase (LPL) hydrolyzes triglyceride in chylomicrons, during the past half decade there has been a reinterest in the physiologic and pathophysiologic actions of this enzyme. In part, this has coincided with clinical studies implicating increased postprandial lipemia as a risk factor for atherosclerosis development. In addition, the recent creation of genetically altered mice with hypertriglyceridemia has focused the interest of geneticists and physiologists on the pathophysiology of triglyceride metabolism. As reviewed in this article, it is apparent that the lipolysis reaction is only partially understood. Several factors other than LPL are critical modulators of this process, in part, because the reaction requires the lipoproteins to interact with the arterial or capillary wall. Among the factors that affect this are the apolipoprotein composition of the particles, the size of the lipoproteins, and how LPL is displayed along the endothelial luminal surface. Zilversmit's observation that LPL activity is found in greater amounts in atherosclerotic than normal arteries has led to a large number of experiments linking LPL with atherogenesis. In medium and large arteries LPL is found on the luminal endothelial surface and in macrophage-rich areas within the plaque. LPL actions in both of these locations probably have major effects on the biology of the blood vessel. Possible atherogenic actions for this LPL based on in vitro experiments are reviewed.
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PMID:Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. 873 71

Within certain limits, it is not possible to screen for asymptomatic early atherosclerotic lesions with the aim of prevention. The effectiveness of different screening tests varies. A vascular murmur has little predictive value. Coronary or aorto-iliofemoral calcifications sometimes occur early. ECG or exertion thallium scan and low distal pressure at rest or during exercise can provide indirect clues as can continuous Doppler or the carotids or peripheral vessels. Pulsed Doppler and color-Doppler are the best screening tools for detecting wall thickening or a silent plaque. Arteriography is essential for patients with coronary artery disease and is often required for carotid or abdominal vessels, but is unfortunately an invasive method and underestimates lesions which do not give a defect image. Angioscopy and endoechography are difficult to manipulate and interpret and cannot be used in routine screening. No biological or genetic markers have been identified as formal indicators of atherosclerosis. Screening is justified in young patients at risk (high blood pressure, intensive smoking, major hyperlipidemia, diabetes, severe family history) because early lesions would lead to a more adapted treatment which can be expected to stabilize or even improve early lesions, or even reduce the risk of plaque rupture. In addition, carotid or iliofemoral lesions increase the risk of coronary artery disease.
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PMID:[Early detection of atherosclerosis]. 875 91

The authors report their experience regarding the identification of Apo-E alleles on atheroma carotid plaques in 20 patients of both sexes diagnosed as suffering from severe carotid stenosis using Doppler tests. A DNA hybridization and amplification method was used to identify Apo E-2, Apo E-3 and Apo E-4 alleles and their various phenotypical combinations. The following results were obtained in the 20 plaques examined: Apo E-3/E-4 in 114 patients (70%), 2 diabetic patients Apo E-4/E-3, one vascular demented patient Apo E-2/E-3, and 3 plaques defined as severely calcified Apo E-2/E-2. It can therefore be seen that the majority of plaques (70%), considered a risk for future stroke due to altered carotid Doppler tests, does not differ greatly by the homozygote allele Apo E-3/E-3 commonly found in the blood of the so-called "normal" population. It is difficult to draw any conclusions from the alleles found in the other 5 patients due to their scarce statistical value and the limited number of carotid plaques examined, but there appears to be some sort of correlation between calcified plaque, hyperlipidemia and the allele Apo E-2/E-2, with an interchange of position between cysteine arginine amino acids in the Apo E sequences.
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PMID:[Atheroma plaque and Apo E alleles]. 876 17


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