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

Atherosclerosis, the precursor of coronary heart disease may originate in childhood. The atherogenic potential of food is related to its cholesterol and saturated-fat content. The study population consisted of children from CHD-parents under the age 12 years with plasma total cholesterol > 170 mg/dl, LDL-Ch > 90 mg/dl and ApoB > 70 mg/dl. All the patients were advised a 6 month diet following National Program of Cholesterol Prevention recommendation. Plasma, TCh, LDL-Ch, ApoB, TG, Ch-esters saturated/unsaturated ratio and platelet factor 4 concentration decreased, LCAT activity and Ch-esters unsaturated increased during study period. We observed interesting correlation between: PF4 and ApoB, PF4 and LDL-Ch and PF4 and HDL-ECh 18:3. Our data show, that proper diet can modify risk factors of CHD in children with family history of CHD.
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PMID:[Effect of dietetic recommendations on the level of some lipid and hemostatic parameters in offspring of parents with risk factors for coronary heart disease]. 908 47

Lipid apheresis, a recently described procedure for the elimination of lipid but not apolipoproteins from plasma, was applied to normocholesterolaemic and hypercholesterolaemic roosters. Lipid apheresis resulted in an immediate reduction in plasma unesterified cholesterol concentration, which was sustained for 150 min. The reduction in unesterified cholesterol concentration was higher in the normocholesterolaemic animals than in the hypercholesterolaemic animals. Lipid apheresis induced changes in the ratio of plasma unesterified to total cholesterol in normocholesterolamic animals but not in hypercholesterolaemic animals. In hypercholesterolaemic animals, lecithin-cholesterol acyltransferase (LCAT) activity was not affected by lipid apheresis, whereas in normocholesterolaemic animals LCAT activity was acutely reduced for 150 min after lipid apheresis. Saturated LCAT kinetics occurred in the hypercholesterolaemic animals but not in the normocholesterolaemic animals. LCAT obeyed Michaelis-Menten kinetics. After lipid apheresis, there was a pool of unesterified cholesterol that was available as substrate for LCAT to a greater extent in hypercholesterolaemic animals than in normocholesterolaemic animals. These observations may have important implications for lipid apheresis as a treatment for atherosclerosis.
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PMID:Lecithin-cholesterol acyltransferase activity in normocholesterolaemic and hypercholesterolaemic roosters: modulation by lipid apheresis. 908 57

Atherosclerosis cardiovascular disease is the leading cause of death in industrial societies. For coronary heart disease, hypercholesterolemia and dyslipoproteinemia are the major risk factors. Low serum levels of cholesterol in the HDL fraction is the most common abnormality found in patients with confirmed coronary artery disease. A therapeutical strategy consists in increasing the serum HDL cholesterol concentration in order to improve the 'reverse cholesterol transport'. Studies in transgenic mice and rabbits for human apo A-I or human lecithin cholesterol acyl-transferase showed that overexpression of these proteins increases serum HDL cholesterol concentration and reduces diet induced atherogenesis. Furthermore, adenovirus-mediated transfer of human apo A-I and LCAT genes in mice also increases circulating apo A-I and LCAT. Apo A-I and LCAT are two potential targets for gene therapy of patients with atherosclerosis associated with a low HDL cholesterol level.
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PMID:High density lipoproteins and coronary heart disease. Future prospects in gene therapy. 958 74

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

A low level of high density lipoprotein (HDL) cholesterol is a strong predictor of ischaemic heart disease (IHD) and myocardial infarction. One cause of low HDL-cholesterol is Tangier disease (TD), an autosomal codominant inherited condition first described in 1961 in two siblings on Tangier Island in the United States of America. Apart from low HDL-cholesterol levels and an increased incidence of atherosclerosis, TD is characterized by reduced total cholesterol, raised triglycerides, peripheral neuropathy and accumulation of cholesteryl esters in macrophages, which causes enlargement of the liver, spleen and tonsils. In contrast to two other monogenic HDL deficiencies in which defects in the plasma proteins apoA-I and LCAT interfere primarily with the formation of HDL (refs 7-10), TD shows a defect in cell signalling and the mobilization of cellular lipids. The genetic defect in TD is unknown, and identification of the Tangier gene will contribute to the understanding of this intracellular pathway and of HDL metabolism and its link with IHD. We report here the localization of the genetic defect in TD to chromosome 9q31, using a genome-wide graphical linkage exclusion strategy in one pedigree, complemented by classical lod score calculations at this region in a total of three pedigrees (combined lod 10.05 at D9S1784). We also provide evidence that TD may be due to a loss-of-function defect.
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PMID:Assignment of Tangier disease to chromosome 9q31 by a graphical linkage exclusion strategy. 973 41

Lipoproteins are spherical macromolecular complexes in which hydrophobic molecules of triglyceride and cholesteryl ester are enveloped within a monolayer of amphipathic molecules of phospholipids, free cholesterol, and apoproteins. The major lipoprotein classes include intestinally derived chylomicrons that transport dietary fats and cholesterol, hepatic-derived VLDL, IDL, and LDL that can be atherogenic, and hepatic- and intestinally derived HDL that are anti-atherogenic. Apoprotein B is necessary for the secretion of chylomicrons (apo B48) and VLDL, IDL, and LDL (apo B100). Post-translational regulation of the assembly of apo B-containing lipoproteins by core lipid availability seems to be the major mechanism for variations in secretion. Plasma levels of VLDL triglycerides are determined mainly by rates of secretion and LPL lipolytic activity; plasma levels of LDL cholesterol are determined mainly by the secretion of apo B100 into plasma, the efficacy with which VLDL are converted to LDL and by LDL receptor-mediated clearance. Regulation of HDL cholesterol levels is complex and is affected by rates of synthesis of its apoproteins, rates of esterification of free cholesterol to cholesteryl ester by LCAT, levels of triglyceride-rich lipoproteins and CETP-mediated transfer of cholesteryl esters from HDL, and clearance from plasma of HDL lipids and apoproteins. Normal lipoprotein transport is associated with low levels of triglycerides and LDL cholesterol and high levels of HDL cholesterol. When lipoprotein transport is abnormal, lipoproteins levels can change in ways that predispose individuals to atherosclerosis.
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PMID:Lipoprotein physiology. 978 50

The aforementioned epidemiological studies have played a central role in defining the importance of plasma lipoprotein disorders in the pathogenesis of atherosclerosis. More specifically, they have been instrumental in establishing plasma lipid and lipoprotein levels such as the plasma concentration of triglyceride, LDL, HDL, and Lp(a), as indicators of CAD risk. The challenge for future epidemiological studies will be to better define the link between CAD and a) the level of particular lipoprotein subfractions, b) factors affecting lipoprotein metabolism, and c) factors affecting the atherogenicity of plasma lipoproteins. For example, it is important to define which triglyceride-rich lipoprotein subfractions are most strongly associated with risk of CAD (e.g., intestinal vs hepatic TRL, large TRL vs smaller TRL remnants) or which subfractions of HDL are most protective (e.g., large vs small HDL, apoE-containing HDL vs apoAI- and All-containing HDL). The relationship between CAD and plasma levels of lipoprotein enzymes and co-factors (e.g., cholesterol ester transfer protein, LCAT), and also compounds that can potentially affect the oxidizability of lipoproteins (e.g., vitamins, paraoxanase) needs to be more clearly defined. Finally, future studies will need to focus not just on the relationship between plasma lipid disorders and atherosclerosis, but between plasma lipids and plaque stability and risk of thrombosis.
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PMID:Plasma triglyceride-rich lipoprotein and high density lipoproteins disorders associated with atherosclerosis. 980 18

This study investigates the suitability of the trimeric apolipoprotein (apo)AI(145-183) peptide that we recently described, to serve as a model to probe the relationship between apoAI structure and function. Three copies of the apoAI(145-183) unit, composed each of two amphipathic alpha-helical segments, were branched onto a covalent core matrix and the construct was recombined with phospholipids. A similar construct was made with the apoAI(102-140) peptide and used as a comparison with dimyristoylglycerophosphocholine (DMPC)-apoAI complexes. The DMPC-trimeric-apoAI(145-183) complexes had similar immunological reactivity with monoclonal antibodies directed against the 149-186 apoAI sequence (A44), suggesting that the A44 epitope is exposed similarly in both the synthetic peptide and the native apoAI complexes. The complexes generated with the trimeric-apoAI(145-183) bind specifically to HeLa cells with comparable affinity to the DMPC apoAI complexes; they are a good competitor for binding of apoAI to both HeLa cells and Fu5AH rat hepatoma cells; finally, these complexes promote cholesterol efflux from Fu5AH cells with an efficiency comparable with the apo AI/lipid complexes. To study LCAT activation by the trimeric apo AI(145-183) construct, complexes were prepared with dipalmitoylphosphatidylcholine (DPPC), cholesterol (C) and either the trimeric construct or apoAI. LCAT activation by the trimeric construct was much lower than by apo AI, possibly because the conformation of the trimeric 145-183 peptide in DPPC/C/peptide complexes does not mimic that of apoAI in the corresponding complexes. In comparison, the complexes generated with the multimeric apoAI(102-140) construct had a poor capacity to mimic the physico-chemical and biological properties of apoAI. The apoAI(102-140) construct had low affinity for lipid compared with the (145-183) construct. After association with lipids, it was a poor competitor of DMPC-apoAI complexes for cellular binding and had only limited capacity to promote cholesterol efflux. These results suggest trimeric constructs can serve as an appropriate models for apoAI, enabling further investigations and new experimental approaches to determine the structure-function relationship of apoAI.
Atherosclerosis 1998 Dec
PMID:Branched synthetic peptide constructs mimic cellular binding and efflux of apolipoprotein AI in reconstituted high density lipoproteins. 986 71

Plasma apolipoprotein AI (apoAI) and lecithin-cholesterol acyltransferase (LCAT) play important roles in reverse cholesterol transport, promoting the removal of excess cholesterol from peripheral cells and reducing formation of atherosclerotic lesions. Gene augmentation of either apoAI or LCAT, or both, are thus attractive targets for prevention or treatment of atherosclerosis. With the eventual aim of safe and efficient gene delivery to skeletal muscle, our chosen secretory platform for systemic delivery of anti-atherogenic proteins, we have constructed conventional and AAV-based plasmid vectors containing human apoAI or LCAT cDNAs; their efficacy was tested by lipoplex transfection of mouse C2C12 muscle cells or human 293 cells. The secretion of apoAI or LCAT by transduced cultures was two- to five-fold higher using AAV-based plasmid vectors than conventional plasmid vectors. Additionally, cells transfected with a bicistronic AAV-based vector containing an internal ribosome entry site (IRES) efficiently expressed both apoAI and LCAT simultaneously. Furthermore, AAV-based vector sequences were retained by host cells, whereas those of conventional plasmid vectors were lost. These studies indicate that ectopic overexpression of apoAI and LCAT in muscle tissue using AAV-based plasmid vectors might provide a feasible anti-atherogenic strategy in vivo.
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PMID:Efficient coexpression and secretion of anti-atherogenic human apolipoprotein AI and lecithin-cholesterol acyltransferase by cultured muscle cells using adeno-associated virus plasmid vectors. 993 Mar 50

The human plasma lipoprotein Lp(a) has gained considerable clinical interest as a genetically determined risk factor for atherosclerotic vascular diseases. Numerous (including prospective) studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke and peripheral atherosclerosis. Lp(a) consists of a large LDL-like particle to which the specific glycoprotein apo(a) is covalently linked. The apo(a) gene is located on chromosome 6 and belongs to a gene family including the highly homologous plasminogen. Lp(a) plasma concentrations are controlled to a large extent by the extremely polymorphic apo(a) gene. More than 30 alleles at this locus determine a size polymorphism. The size of the apo(a) isoform is inversely correlated with Lp(a) plasma concentrations, which are non-normally distributed in most populations. To a minor extent, apo(a) gene-independent effects also influence Lp(a) concentrations. These include diet, hormonal status and diseases like renal disease and familial hypercholesterolemia. The standardisation of Lp(a) quantification is still an unresolved problem due to the enormous particle heterogeneity of Lp(a) and homologies of other members of the gene family. Stability problems of Lp(a) as well as statistical pitfalls in studies with small group sizes have created conflicting results. The apo(a)/Lp(a) secretion from hepatocytes is regulated at various levels including postranslationally by apo(a) isoform-dependent prolonged retention in the endoplasmic reticulum. This mechanism can partly explain the inverse correlation between apo(a) size and plasma concentrations. According to numerous investigations, Lp(a) is assembled extracellularly from separately secreted apo(a) and LDL. The sites and mechanisms of Lp(a) removal from plasma are only poorly understood. The human kidney seems to represent a major catabolic organ for Lp(a) uptake. The underlying mechanism is rather unclear; several candidate receptors from the LDL-receptor gene family do not or poorly bind Lp(a) in vitro. Lp(a) plasma levels are elevated over controls in patients with renal diseases like nephrotic syndrome and end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus mainly result from insufficient sample sizes in numerous studies. Large studies and those including apo(a) phenotype analysis have come to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In non-insulin-dependent diabetics Lp(a) is not elevated. Several rare disorders, such as LCAT and LPL deficiency, as well as liver diseases and abetalipoproteinemia are associated with low plasma levels or lack of Lp(a).
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PMID:Genetics and metabolism of lipoprotein(a) and their clinical implications (Part 1). 1006 65


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