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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transfer of low-density lipoprotein (L.D.L.2) from plasma to arterial intima was studied in 16 patients undergoing arterial surgery. Autologous labelled lipoprotein was used to demonstrate that L.D.L.2 enters the intima from plasma. Net flux of L.D.L.2 appeared to increase with age. Within each age-group the net flux of L.D.L.2 showed a pronounced positive correlation with plasma-L.D.L.-cholesterol concentrations. This may account in part for the association between hypercholesterolaemia and the development of atherosclerosis.
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PMID:Influence of lipid concentrations and age on transfer of plasma lipoprotein into human arterial intima. 7 Jun 86

Groups of rats were fed diets containing either butter, beef, fat or safflower oil. After 20 or 70 days of feeding, blood was taken from the animals in a postabsorptive state. Serum lipid levels and lecithin: cholesterol acyl transferase activity were measured. Feeding the different fats did not alter serum total cholesterol levels but free cholesterol and triglycerides were significantly lower in the safflower oil-fed group. Net cholesterol esterification in vitro was also significantly depressed in the safflower oil-fed group and this was shown to be due to the inability of the lipoprotein substrate to support the reaction rather than because of low LCAT enzyme activity.
Atherosclerosis 1977 Feb
PMID:Lecithin: cholesterol acyl transferase activity in the serum of rats fed saturated and unsaturated fats. 83 58

Rupture of plaques followed by thrombosis and thrombo- or atheroembolism mark the clinical horizon of ischemic organ lesions in atherosclerosis. Initiation and development of lesions precede these often dramatic events by decades. Precursor lesions arise within the first, irreversible ones may develop from the second decade of life onwards. Two concurring or succeeding pathogenetic mechanisms dominate: 1. Discrete or functional endothelial injury (in conjunction with hemodynamic wall stresses and effects of endogenous or exogenous toxic factors such as hormones, immune- and other mediators, components of tobacco smoke, etc.) induces increased flow of low density lipoprotein (LDL) into arterial tissue. Immigrating monocytes capture LDL and accumulate its cholesterol as ester droplets becoming foam cells. Net flux and accumulation of cholesterol probably correlate with plasmatic LDL-cholesterol levels. 2. Endothelial denudation, also occurring under the influence of mechanical wall stresses and in particular over precursor lesions, incites platelet aggregation and clotting mechanisms. As a consequence, arterial smooth muscle proliferates in the sense of repair of injury, resulting in the formation of scar tissue. Lipid-rich lesions with scanty scars seem to be particularly prone to rupture and thus important complications. Plaque rupture is probably the most common complication leading to ischemic disease, whereby the extent of formation and organisation of thrombi might determine whether infarction or chronic ischemia is the outcome.
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PMID:[Current concepts of the pathogenesis of atherosclerosis]. 259 58

Lipid accumulation in the human aorta occurs predominantly downstream of branches in foetuses, neonates and infants but upstream at later ages. The lipid in these deposits may derive from plasma lipoproteins. We have examined uptake of plasma proteins by the rabbit aortic wall near branches as a function of age. Albumin was labelled with a fluorescent dye and introduced into the circulation of animals fed a normal diet. The aorta was fixed in situ 3 h later and the distribution of tracer in sections through the wall was measured by using digital imaging fluorescence microscopy. Net uptake by the intima-media was higher downstream of intercostal ostia than upstream in young animals but this difference decreased and then reversed with age. Furthermore, the average of uptake by both regions was higher shortly after weaning than at later ages. These age-related variations in transport properties may explain discrepancies between previous studies of uptake, resolve apparent inconsistencies between the properties of rabbit and human arteries and, if applicable to man, might account for the non-uniform and changing pattern of lipid accumulation around arterial branches.
Atherosclerosis 1994 Mar
PMID:Age-related variations in transport properties of the rabbit arterial wall near branches. 801 1

Cholesteryl esters (CE) exchange between lipoproteins through the action of cholesteryl ester transfer protein (CETP). Situations at high risk for atherosclerosis are often accompanied by an accelerated net mass CE transfer (CET) from high density lipoproteins (HDL) to very low (VLDL) and low density lipoproteins (LDL). However, the question as to whether the net mass CET is increased or decreased in non-insulin-dependent diabetes mellitus (NIDDM) has led to controversial data. To clarify this point, we have undertaken a detailed study of CET in 105 NIDDM patients by comparison with 17 control subjects. Net mass CET was approximately doubled in NIDDM. Plasma CETP activity and unidirectional CET from HDL to VLDL + LDL (CETHDL-->VLDL + LDL) or from VLDL + LDL to HDL (CETVLDL + LDL-->HDL) were measured under controlled lipoprotein concentrations using radioisotopic assays. No difference was observed in plasma CETP activity between NIDDM and controls. In NIDDM, CETHDL-->VLDL + LDL and CETVLDL + LDL-->HDL were decreased by 25% and 20%, respectively, as a consequence of alterations in lipoprotein compositions. Net mass CET was highly correlated with plasma triglyceride (TG) concentration (r = 0.66, P < 0.001) but not with that of LDL-cholesterol (r = 0.06, P > 0.6). When TG levels were decreased following dietetic recommendations or insulinotherapy, the net mass CET was lowered accordingly. We conclude that net mass CET is accelerated in NIDDM in spite of a decreased unidirectional CETHDL-->VLDL + LDL. This results from a lowered CETVLDL + LDL-->HDL and from elevated TG concentration, and the latter probably reflects a concentration effect of VLDL.
Atherosclerosis 1996 Jun
PMID:Alterations in composition and concentration of lipoproteins and elevated cholesteryl ester transfer in non-insulin-dependent diabetes mellitus (NIDDM). 878 40

Abnormalities in cholesteryl ester transfers may play a role in the development of atherosclerosis observed in patients with end-stage renal failure treated by chronic hemodialysis. Net neutral-lipid transfers and cholesteryl ester transfer protein activity and mass were investigated in 20 hemodialyzed patients, arbitrarily divided into two groups based on fasting triglyceride levels, and compared to triglyceride-matched control groups. In the hypertriglyceridemic subjects (plasma triglyceride values > 150 mg/dl), high-density lipoprotein cholesterol was decreased, and the net cholesteryl ester transfer rates were significantly higher than the rates in normolipidemic subjects. The comparison of subjects matched for plasma triglyceride and cholesterol levels showed no significant difference in cholesteryl ester or triglyceride transfer rates between patients and controls. Our results suggest that normal or elevated net neutral-lipid transfers are not related to the renal status of the subjects, but rather to their plasma triglyceride levels.
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PMID:Neutral-lipid transfers and cholesteryl ester transfer protein in hemodialyzed patients. 888 76

The participation of HDL in the reverse cholesterol transport (RCT) from peripheral cells to the liver is critical for the antiatherogenic properties of this lipoprotein. Experimental results showing that efflux of cholesterol from cells growing in culture is mediated by HDL and lipoprotein particles containing apo A-I, in particular, support this conclusion. A bidirectional flux of unesterified cholesterol molecules between the plasma membrane of cells and HDL particles in the extracellular medium occurs. Net efflux of cholesterol mass from the cells involves passive diffusion of cholesterol molecules through the aqueous phase and down their concentration gradient between the membrane and HDL; the concentration gradient is maintained by LCAT-mediated esterification of cholesterol molecules in the HDL particles. Fully lipidated apo A-I is important in promoting this aqueous diffusion mechanism because it: (1) acts as a cofactor for LCAT; and (2) solubilizes phospholipid into small HDL-sized particles that are efficient at absorbing cholesterol molecules diffusing away from the cell surface. Apo A-I also exists in an incompletely lipidated state in plasma. Apo A-I molecules in this state are able to solubilize phospholipid and cholesterol from the plasma membrane of cells. This membrane-microsolubilization process is enhanced by enrichment of the plasma membrane with cholesterol and is the mechanism by which pre-beta-HDL particles in the extracellular medium remove cholesterol and phospholipid from cells. The relative contributions in vivo of the aqueous diffusion and membrane-microsolubilization mechanisms of apo A-I-mediated cell cholesterol efflux are not predicted readily from cell culture experiments. Confounding issues are the variations with cell type and the dependence on the degree of cholesterol loading of the cell plasma membrane.
Atherosclerosis 1998 Apr
PMID:Mechanisms of high density lipoprotein-mediated efflux of cholesterol from cell plasma membranes. 969 36

The ternary complex factors (TCFs) Net, Elk-1 and Sap-1 regulate immediate early genes through serum response elements (SREs) in vitro, but, surprisingly, their in vivo roles are unknown. Net is a repressor that is expressed in sites of vasculogenesis during mouse development. We have made gene-targeted mice that express a hypomorphic mutant of Net, Net delta, which lacks the Ets DNA-binding domain. Strikingly, homozygous mutant mice develop a vascular defect and up-regulate an immediate early gene implicated in vascular disease, egr-1. They die after birth due to respiratory failure, resulting from the accumulation of chyle in the thoracic cage (chylothorax). The mice have dilated lymphatic vessels (lymphangiectasis) as early as E16.5. Interestingly, they express more egr-1 in heart and pulmonary arteries at E18.5. Net negatively regulates the egr-1 promoter and binds specifically to SRE-5. Egr-1 has been associated with pathologies involving vascular stenosis (e.g. atherosclerosis), and here egr-1 dysfunction could possibly be associated with obstructions that ultimately affect the lymphatics. These results show that Net is involved in vascular biology and egr-1 regulation in vivo.
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PMID:Net-targeted mutant mice develop a vascular phenotype and up-regulate egr-1. 1156 78

Atherosclerotic arteries frequently become calcified, and these calcium deposits are associated with a high risk of adverse clinical events. Descriptive studies suggest calcification is an organized and regulated process with many similarities to osteogenesis, yet the mechanism and its relationship to atherosclerosis remain largely unknown. In bone development and homeostasis, mineral deposition by osteoblasts and mineral resorption by osteoclasts are delicately balanced such that there is no overall gain or loss in bone mass. We hypothesize that there exists in arteries a mechanism that similarly balances mineral deposition with resorption. We propose that the cellular mediators of arterial mineral resorption are osteoclast-like cells (OLCs) derived from hematopoietic precursors of the mononuclear phagocytic lineage. In arterial microenvironments, mononuclear precursors are induced to differentiate toward OLCs by macrophage-colony stimulating factor and receptor activator of NF-kappaB ligand, both of which are necessary and sufficient for osteoclastogenesis and mineral resorption in bone. OLCs may participate in normal mineral homeostasis within the arterial wall or, alternatively, may be recruited to specific sites within developing plaque. Net calcium deposition occurs as a result of focal perturbation of the balance between the activity of osteoblast-like cells and OLCs. Our proposed mechanism thus views arterial mineral deposition not so much as an active pathological process, but as a localized failure of protective mechanisms that actively oppose mineral deposition within the disordered metabolic milieu of developing atherosclerotic plaque.
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PMID:Rationale for the role of osteoclast-like cells in arterial calcification. 1191 60

Net reclassification has become widely accepted as a method to demonstrate whether new diagnostic technologies add significantly to the discrimination of risk. However, more accurate categorization of risk does not necessarily result in a better clinical outcome. This study examined whether coronary artery calcium, a technology that improves net reclassification in patients at intermediate risk for cardiovascular events, is superior to a strategy that calls for broader intervention with statin therapy in these patients. To do so, the clinical impact and costs of 2 intervention regimens on outcome in the Multi-Ethnic Study of Atherosclerosis (MESA) were calculated based on the known efficacy of statins. Intervention 1 involved treatment of all subjects at conventional intermediate risk with moderate-dose stain, whereas intervention 2 involved moderate- and high-dose statin therapy, respectively, of those remaining at intermediate risk and those reassigned to high risk after reclassification by coronary artery calcium. The 2 strategies would decrease clinical events by 23% and would produce net savings. However, these would be greater with the broad statin prevention strategy than with the coronary calcium reclassification strategy ($732,152 vs $288,336, respectively). In conclusion, even in the short term, the broad statin prevention strategy would be at least as effective in decreasing clinical events but with greater net savings than a prevention strategy using coronary calcium screening.
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PMID:Comparison of coronary calcium screening versus broad statin therapy for patients at intermediate cardiovascular risk. 2257 82


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