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

Thrombotic occlusion is the major cause of myocardial infarction (MI), and fibrin accumulation appears to play a significant role in development of atherosclerotic lesions. Any factor that reduces the lysis of fibrin may thus increase the risk of MI, and it has been suggested that this accounts for the atherogenicity of the lipoprotein variant Lp(a). The characteristic feature of Lp(a) is an apoprotein which is homologous with part of the plasminogen molecule, and experiments in vitro suggest that it interferes with uptake and activation of plasminogen on cell surfaces and fibrin. The presence of Lp(a) also seemed to offer an explanation for the apparent absence of plasminogen from 70-80% of intimal samples. We have compared the levels of Lp(a) and plasminogen in normal intima and atherosclerotic lesions. In aortic intima there was no relation between Lp(a) and plasminogen, which was absent in some samples with no Lp(a), and present in others with high levels. In intravascular thrombi plasminogen was present at a rather constant concentration (16.3 +/- 4.6 micrograms/100 mg wet tissue), whereas Lp(a) varied over a 100 fold range (0-104 micrograms/100 mg). Plasminogen binds to fibrin and is activated on the fibrin clot, so levels in extracts may not fully represent Lp(a)/plasminogen interactions. After extraction the residual tissues and thrombi were treated with 1 M epsilon-aminocaproic acid (epsilon-aca) to elute lysine-bound components. Lp(a) was eluted from all but one intimal sample, confirming previous findings on its binding to fibrin in lesions, but there was no relation between the amounts of Lp(a) and plasminogen in the tissue eluates. Paradoxically, in the thrombi there was a weak positive correlation between Lp(a) and plasminogen in epsilon-aca eluates (r = 0.504, P = 0.05). These results do not support the hypothesis that Lp(a) displaces plasminogen in vivo, but the large amount of Lp(a) eluted by epsilon-aca suggests that its atherogenicity resides in preferential binding to fibrin, leading to increased lipid accumulation in lesions.
Atherosclerosis 1991 Aug
PMID:Does lipoprotein(a) (Lp(a)) complete with plasminogen in human atherosclerotic lesions and thrombi? 183 24

Inbred mouse strains C57BL/6J (B6) (susceptible) and C3H/HeJ (C3H) (resistant) differ in atherosclerosis susceptibility due to a single gene, Ath-1. Plasma lipoproteins from female mice fed chow or an atherogenic diet displayed strain differences in lipoprotein particle sizes and apolipoprotein (apo) composition. High density lipoprotein (HDL) particle sizes were 9.5 +/- 0.1 nm for B6 and 10.2 +/- 0.1 nm for C3H. No major HDL particle size subclasses were observed. Plasma HDL level in the B6 strain was reduced by the atherogenic diet consumption while the HDL level in the resistant C3H mice was unaffected. The reduction in HDL in the B6 strain was associated with decreases in HDL apolipoproteins A-I(-34%) and A-II(-60%). The HDL apoC content in mice fed chow was two-fold higher in C3H than B6. Lipoproteins containing apolipoprotein B (VLDL, IDL, LDL) shifted from a preponderance of the B-100 (chow diet) to a preponderance of the B-48 (atherogenic diet). The LDL-particle size distribution was strain-specific with the chow diet but not genetically associated with the Ath-1 gene. In both strains on each diet, apolipoprotein E was largely distributed in the VLDL, LDL, and HDL fractions. The B6 strain became sixfold elevated in total lipoprotein E content which in the C3H strain was not significantly affected by diet. However, the C3H LDL apoE content was reduced. On both diets, the C3H strain exhibited apolipoprotein E levels comparable to the atherogenic diet-induced levels of the B6 mice.
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PMID:Effects of atherogenic diet consumption on lipoproteins in mouse strains C57BL/6 and C3H. 185 5

Various types of studies in humans and animals suggest strongly that HDL is anti-atherogenic. The anti-atherogenic potential of HDL is thought to be due to its participation in reverse cholesterol transport, the process by which cholesterol is removed from non-hepatic cells and transported to the liver for elimination from the body. Extensive studies in cell culture systems have demonstrated that HDL is an important mediator of sterol transport between cells and the plasma compartment. The topic of this review is the mechanisms that account for sterol movement between HDL and cells. The most prominent and easily measured aspect of sterol movement between HDL and cells is the rapid bidirectional transfer of cholesterol between the lipoprotein and the plasma membrane. This movement occurs by unmediated diffusion, and in most situations its rate in each direction is limited by the rate of desorption of sterol molecules from the donor surface into the adjacent water phase. The net transfer of sterol mass out of cells occurs when there is either a relative enrichment of sterol within the plasma membrane or a depletion of sterol in HDL. Recent studies suggest that certain minor subfractions of HDL (with pre-beta mobility on agarose gel electrophoresis and containing apoprotein A-I but no apo A-II) are unusually efficient at promoting efflux of cell sterol. To what extent efflux to these HDL fractions is balanced by influx from the lipoprotein has not yet been established clearly. The prevention and reversal of atherosclerosis require the mobilization of cholesterol from internal (non-plasma membrane) cellular locations. To some extent, this may involve the retroendocytosis of HDL. However, most mobilization probably involves the transport of internal sterol to the plasma membrane, followed by desorption to extracellular HDL. Several laboratories are investigating the transport of sterol from intracellular locations to the plasma membrane. Studies on biosynthetic sterol (probably originating mostly in the smooth endoplasmic reticulum) suggest that there is rapid transport to the plasma membrane in lipid-rich vesicles. Important features of this transport are that it bypasses the Golgi apparatus and may be positively regulated by the specific binding of HDL to the plasma membrane.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cholesterol transport between cells and high-density lipoproteins. 191 62

A cDNA clone containing the coding region for cynomolgus monkey cholesteryl ester transfer protein (CETP) was isolated by the polymerase chain reaction with primers based on the human CETP cDNA sequence and cDNA synthesized from liver poly (A+) RNA. Analysis of that cDNA indicated that the nucleotide and amino acid sequences of cynomolgus monkey CETP were greater than 95% homologous with the human sequences. A fragment of the cDNA was used to develop an internal-standard/RNAse protection assay that allowed precise quantification of CETP mRNA levels. Analysis of total RNA from various tissues with this assay revealed that the liver and thoracic aorta expressed high levels of CETP mRNA; the mesenteric fat, adrenal gland, spleen, and abdominal aorta had low but detectable levels of the mRNA; and the brain, kidney, intestine, and skeletal muscle had undetectable levels of that mRNA. When the monkeys were made hypercholesterolemic by a high-fat, high-cholesterol (HFHC) diet, hepatic levels of CETP mRNA increased from 1.6 +/- 0.4 pg/micrograms total RNA (mean +/- SEM) to 4.1 +/- 0.8 pg/micrograms (p less than 0.005); mesenteric fat CETP mRNA increased from 0.4 +/- 0.1 pg/micrograms total RNA to 5.3 +/- 2.2 pg/micrograms (p less than 0.05); and plasma CET activity increased approximately fourfold. The CETP mRNA levels in the thoracic and abdominal aortas were not significantly increased in monkeys fed the HFHC diet, even though those animals had gross atherosclerosis. The apoprotein E mRNA levels, however, were markedly increased in the aortas of monkeys with atherosclerosis, with the largest increase occurring in the abdominal aorta. Taken together, these data suggest that lipid deposition in the artery was not accompanied by increased expression of the CETP gene in that tissue. Statistical analysis showed that a strong, negative correlation existed between hepatic CETP mRNA levels and both high density lipoprotein cholesterol (r = -0.85, p less than 0.001) and apoprotein A-I (r = -0.84, p less than 0.001). These data suggest that HFHC diet-induced changes in high density lipoprotein metabolism may be linked to altered expression of a function CETP gene.
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PMID:Molecular cloning, sequence, and expression of cynomolgus monkey cholesteryl ester transfer protein. Inverse correlation between hepatic cholesteryl ester transfer protein mRNA levels and plasma high density lipoprotein levels. 193 78

High-density lipoprotein (HDL) cholesterol levels have an inverse relationship with the frequency of coronary and cerebrovascular disease. Most commonly HDL deficiency is environmentally modulated. Familial hypoalphalipoproteinemia (FHA) is a genetically determined HDL deficiency disease, in all likelihood transmitted as an autosomal dominant trait and associated with premature atherosclerosis. Apolipoprotein AI (apo AI) is the major apoprotein in the HDL particle, and defects in this protein have been suggested as the cause of FHA. We have identified a large family of Spanish descent with FHA and performed genetic linkage analysis using restriction fragment length polymorphisms in the Apo AI-CIII-AIV gene cluster to test this hypothesis. Results in this family formally exclude the apo AI-CIII-AIV gene cluster as the site for the mutation underlying FHA.
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PMID:The gene causing familial hypoalphalipoproteinemia is not caused by a defect in the apo AI-CIII-AIV gene cluster in a Spanish family. 196 39

Dysbetalipoproteinaemia is a genetic disorder characterized by accumulation of lipoprotein remnant particles in the plasma, accelerated atherosclerosis, and the abnormal apoprotein E2. Uncontrolled diabetes mellitus can aggravate the hyperlipidaemia associated with this disorder, presumably by increasing triglyceride synthesis and reducing very low density lipoprotein catabolism by lipoprotein lipase. This report documents the gradual amelioration of dysbetalipoproteinaemia in uncontrolled diabetes mellitus following therapy with exogenous insulin alone. Although the beneficial effects of insulin therapy in this patient may include inhibition of triglyceride synthesis and improved triglyceride catabolism, we propose that insulin may also stimulate clearance of atherogenic remnant lipoprotein particles.
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PMID:Potential role of insulin in the clearance of remnant lipoproteins in dysbetalipoproteinaemia. 199 70

A multicentre study on atherosclerosis precursors in young Finns aged three to 18 years was started in 1980 (3596 subjects) serum lipid concentrations (cholesterol, HDL (high density lipoprotein) cholesterol and triglycerides) were determined (n = 3554) and the apolipoproteins A-I and B measured (n = 1355). Two follow-up studies were carried out in 1983 (n = 2851) and 1986 (n = 2489), when HDL-subfractions (HDL-2-cholesterol and HDL-3-cholesterol) were also determined. Apolipoproteins A-I and B were measured again in 1986 (n = 1202). Serum total cholesterol concentration has fallen by about 1% annually during the 1980's from 5.07 mmol/l (1980) to 4.79 mmol/l (1986) in 9- to 18-year old children and adolescents. Mean values of serum triglycerides have slightly increased during the follow-up from 0.79 mmol/l to 0.84 mmol/l, respectively. In children and young adults (3-24 years) the mean cholesterol concentration was highest at the age of six and lowest during puberty. Concentrations of serum cholesterol, LDL (low density lipoprotein) cholesterol apoprotein B and triglycerides were higher in eastern than in western Finland in 1980 and 1983, but these differences were smaller in 1986, with the exception of serum triglycerides. Both in 1983 and in 1986 HDL-2-cholesterol was lower in the west than in the east, whereas HDL-3-cholesterol was higher in the former. The favourable changes in lipid levels should be reflected in future morbidity and mortality rates from coronary heart disease in Finland.
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PMID:Serum lipids and lipoproteins in children, adolescents and young adults in 1980-1986. 203 6

The authors provide the data on the central hemodynamics, blood plasma lipoproteins and apoproteins in 101 adolescents with aggravated heredity as regards coronary heart disease and in healthy adolescents of the same age serving as control. The hypokinetic variant of circulation is demonstrated to be coupled with the atherogenic nature of the lipoprotein and apoprotein spectra and heredity to contribute greatly to the traits under study. Criteria for the adolescents' inclusion into the group at the highest risk for early development of atherosclerosis are described.
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PMID:[Changes in central hemodynamics as a risk factor of the development of ischemic heart disease in adolescents with aggravated heredity of atherosclerosis]. 204 76

There is agreement about the influence of the genetic apolipoprotein (apo E) polymorphism on plasma lipid and apoprotein levels in man. Whereas the association of the apo E2 isoform with primary dysbetalipoproteinemia and hyperlipoproteinemia type III is well established, the plasma- and LDL-cholesterol lowering effects of apo E2 and the phenomenon of apo E4 raising these parameters on the development of coronary heart disease is still a matter of controversial discussion. Despite these uncertainties the knowledge of an individual's apo E phenotype may provide additional information in future to judge its risk to develop atherosclerosis. From a variety of methods meanwhile described to analyze the polymorphism and evaluate the apo E phenotype the author has modified three procedures to apply to different questions concerning apo E isoform analysis. They concern the visualization of the apo E pattern in diluted solutions and those containing high salt concentrations, the apo E phenotyping on a large scale basis from whole plasma avoiding a possible misinterpretation by a thrombin fragment of apo E and finally the search for new apo E variants with a high resolution system on immobilized pH gradient gels.
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PMID:Clinical implications of the apolipoprotein E polymorphism and genetic variants: current methods for apo E phenotyping. 204 69

Human apolipoprotein E, a blood plasma protein, mediates the transport and uptake of cholesterol and lipid by way of its high affinity interaction with different cellular receptors, including the low-density lipoprotein (LDL) receptor. The three-dimensional structure of the LDL receptor-binding domain of apoE has been determined at 2.5 angstrom resolution by x-ray crystallography. The protein forms an unusually elongated (65 angstroms) four-helix bundle, with the helices apparently stabilized by a tightly packed hydrophobic core that includes leucine zipper-type interactions and by numerous salt bridges on the mostly charged surface. Basic amino acids important for LDL receptor binding are clustered into a surface patch on one long helix. This structure provides the basis for understanding the behavior of naturally occurring mutants that can lead to atherosclerosis.
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PMID:Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E. 206 94


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