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

The application of molecular biology techniques has enabled us to determine the gene sequence, organization, transcription and processing of apolipoprotein genes. Consequently, new insights have been gained in the biosynthesis and processing of these proteins. In addition to apoA-I, apoA-II and apoC-III reported here, other apolipoprotein genes such as apoC-II and apoE genes were found to share common intron-exon organizations. The results suggest that these genes most probably arise from a common ancestral gene. Utilizing cDNA as hybridization probes, we have localized apoA-I, apoA-II, apoC-II, apoC-III, apoE and apoB to specific locations of individual chromosomes (for review, see ref. 6). There is no clear relationship between currently known physiological function and the organization of the apolipoproteins in the chromosomes with the exception of the LDL receptor and its ligand, apoE which are localized to chromosome 19. However, apoB-100, the major ligand for the LDL receptor is on chromosome 2 and not in synteny with the apoE and the LDL receptor genes. The cloning of the major human apolipoprotein genes have also allowed us to initiate studies on the molecular defects leading to various dyslipoproteinemias including Tangier disease and abetalipoproteinemia. Undoubtedly, information derived from these studies will provide the basis for future in vitro and in vivo studies on patients with dyslipoproteinemia and premature atherosclerosis.
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PMID:The molecular biology of human apoA-I, apoA-II, apoC-II and apoB. 243 61

We studied the biochemical and biological properties of plasma lipoproteins taken from blood derived from either the aorta or femoral vein of patients with normal coronary arteriography. There were no significant differences in concentrations of cholesterol, triglycerides, apoprotein A-1 and apoprotein B derived from either source. The cholesterol content of very low density lipoprotein (VLDL) and high density lipoprotein (HDL) was similar in both aortic and venous blood. The low density lipoprotein (LDL) concentration, however, was significantly higher in the aortic blood sample. Arterial LDL significantly enhanced in vitro platelet aggregation when compared to venous LDL. (p less than 0.02). When incubated with mouse peritoneal macrophages (MPM) arterial LDL and VLDL caused an increased cholesterol accumulation and enhanced cholesterol esterification within these macrophages. The venous lipoproteins had little effect. The differences noted in the arterial lipoproteins in composition and biological function when compared to venous lipoproteins might be related to the much higher incidence of atherosclerosis found in the arterial tree.
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PMID:Arterial blood derived low density lipoprotein increases platelet aggregation and macrophage cholesterol content in comparison to lipoprotein derived from veinous blood. 249 79

We have employed immunoaffinity chromatography to characterize the distribution of cholesteryl ester transfer activity in particles secreted by HepG2 hepatocytes. HepG2-secreted cholesteryl ester transfer activity is associated with apoprotein (apo) A-I (58%) as well as apo A-II (55%), and is not associated with apo B or E. In contrast, our previous studies have shown that most (88%) cholesteryl ester transfer activity in human plasma is associated with apo A-I whereas very little (7%) is associated with apo A-II. Thus, the distribution of cholesteryl ester transfer activity in plasma particles likely reflects active remodeling of nascent particles in the plasma compartment. Further data suggested that HepG2 cells secrete a lipid transfer inhibitor activity which is associated with apo E-containing lipoprotein particles. This inhibitory activity is heat labile.
Atherosclerosis 1989 May
PMID:Secretion of cholesteryl ester transfer protein-lipoprotein complexes by human HepG2 hepatocytes. 249 52

Lipoprotein(a) (Lp(a)) has been strongly linked with atherosclerosis and is an independent risk factor for myocardial infarction. Distinguishing Lp(a) from other low-density lipoprotein particles is its content of a unique apoprotein, apo(a). The recently described sequence of apo(a) indicates a remarkable homology with plasminogen, the zymogen of the primary thrombolytic enzyme, plasmin. Lp(a) may contain 37 or more disulphide-looped kringle structures, which are 75-85% identical to the fourth kringle of plasminogen. Plasminogen receptors are widely distributed on blood cells and are present at extremely high density on endothelial cells. These receptors promote thrombolysis by accelerating plasminogen activation and protecting plasmin from inhibition. If, by molecular mimicry, Lp(a) competes with plasminogen for receptors, then thrombolysis would be inhibited and thrombosis promoted. Here we provide support for such a mechanism being responsible for the thrombotic risks associated with elevated Lp(a) by demonstrating that Lp(a) inhibits plasminogen binding to cells.
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PMID:A potential basis for the thrombotic risks associated with lipoprotein(a). 254 96

The whole lipoprotein spectrum of human plasma may be divided into atherosclerotic and anti-atherosclerotic lipoproteins. To the first class belong apolipoprotein (apo) B and some apoE-containing lipoproteins of the very-low-density (VLDL), intermediate-density (IDL) and low-density (LDL) lipoprotein fractions. Anti-atherosclerotic lipoproteins are apoA-containing high-density lipoproteins (HDL). Circulating plasma lipoproteins are catabolized mainly by specific cell surface receptors (R) which react with apoB and apoE (B/E-R), for apoE (E-R) or for apoA (HDL-R). Whereas the B/E-R and E-R are responsible for the cellular uptake of lipoproteins and their lipid load by various organs, HDL-R are thought to promote lipid (cholesterol) efflux. There is an additional class of lipoprotein receptors, the so called scavenger-R which are responsible for the removal of altered or degraded lipoproteins for the circulation. Under normal physiological conditions, the concerted action of these receptors warrants efficient lipoprotein turnover and direction into target organs. Derangements of this system, however, may lead to the deposition and accumulation of atherogenic lipids, notably free cholesterol (FC) and cholesteryl esters (CE) in arterial tissue causing atherosclerosis and cardiac death.
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PMID:Lipoprotein receptors and atherosclerosis. 254 4

The structure of lipoproteins is described, followed by a description of the structure and function of low density lipoproteins (LDL) which carry cholesterol to cells, and high density lipoproteins (HDL) which remove cholesterol. The process of atherosclerosis is then indicated. When LDL accumulates in plasma, it is deposited in macrophages which metabolize all the components of LDL except the cholesterol ester which becomes a foam cell. HDL converts foam cells back to macrophages. The presence of HDL and HDL2 allows foam cells to secrete cytoplasmic cholesterol and an apoprotein E which coats HDL2 and allows the recognition and removal of cholesterol in blood and by receptors in he liver. Atherosclerosis can be predicted from the effect of the HDL and LDL on foam cell formation, i.e., more foam cells means more HDL, particularly HDL2, and the less likely atherosclerosis will develop. The link between oral contraceptives (OCs) and atherosclerosis is that with estrogen LDL cholesterol levels decrease, while there are increases with progestins; HDL and HDL2 increase with estrogen and decrease with progestins. HDL3 is unaffected by estrogen. The effects of progestins are dependent on a number of other factors. Longterm clinical trials of OCs and their effects on lipoproteins are identified from Johns Hopkins and George Washington University studies. The longterm trail results are given. Total cholesterol rose regardless of the 3 different progestins. Compounds containing dl-norgestrel in higher doses raised LDL levels more than ethynodiol diacetate or norethindrone. In low doses, levels of LDL also rose but ethynodiol diacetate rose least in 6 months. Apoprotein B also rose in a similar fashion. Norgestrel lowers HDL considerably and HDL2 in higher or lower doses; there were more differences in ethynodiol diacetate or norethindrone. All 3 preparations raised HDL3 similarly. Norgestrel decreases apoprotein levels in high doses and apoprotein is unaffected at low doses; low apoprotein is linked to coronary artery disease. Increases occurred with ethynodiol diacetate and norethindrone. New triphasic compounds are under investigation, and show low HDL at 6 but not 12 months, but consistently raise LDL. Lipoprotein phospholipids research findings are also revealed as well as other related research. Adverse effects may be seen for many years after OC use, so low doses are recommended.
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PMID:Effects of oral contraceptives on circulating lipids and lipoproteins: maximizing benefit, minimizing risk. 257 64

Risk factors for atherosclerosis in children were studied in families where the father had suffered from myocardial infarction before the age of 45 years and in the families of the closest relatives. The values of metabolism of lipids and atherogenic indexes were compared with the findings in a series of children with no positive family history. In children of at risk families cholesterol and triglyceride values were increased in 34.3%, HDLc was decreased in 42.1%, and apoprotein B was increased in 53.1%. Of the atherogenic indexes the LDL/HDL ratio proved to be the most significant. More than half of the children from at risk families can be considered to be threatened with atherogenesis. These children have to be followed up regularly and great care is to be given to a proper regimen.
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PMID:[Risk factors for cardiovascular diseases in childhood]. 259 Aug 51

Comparison of a group of adolescents aged 11-16 years whose fathers had angiographically documented coronary atherosclerosis in youth with those matched by sex and age whose parents were clinically healthy yielded the following discriminant function (DF) involving lipid and apoprotein indices of the plasma lipid system: DF = [apo B] X 0.03-[HDL cholesterol] X 0.04-0.81. DF greater than or equal to 0 discriminates from the controls 32% of the offsprings from the fathers with a history, DF less than 0 correctly classifies 98% of adolescents from the controls. The adolescents who have DF greater than or equal to 0 amounted to about 19% in representative samples of Moscow adolescents. Moreover, DF with 80% probability makes it possible to predict the time course of serum lipid levels in adolescents within 2 years.
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PMID:[Atherogenic dyslipidemia in adolescents: its relation to ischemic heart disease in their fathers and the possibility of its prognosis]. 259 69

The reduction of total and LDL cholesterol (TC and LDLc), apoprotein B (ApoB) and in some instances triglycerides (TG) and the increase of HDL cholesterol (HDLc) and apoprotein A (ApoA) seem to be associated to a reduced coronary risk. Aim of our work was to evaluate the effects of a chronic treatment with the HMG-CoA reductase inhibitor simvastatin (MK-733), in a group of 8 dyslipidemic patients, 5 women and 3 men, aged between 48 and 69 years (mean age 59 +/- 8 years) at high risk being already affected by clinical compliances of atherosclerosis and not previously controlled by diet and/or other antidyslipidemic drugs. At the beginning and at the end (6 months) of this open study it was performed a clinical, ECG and ophthalmological examination, as well as an evaluation of the routine laboratory parameters. The initial dosage of simvastatin was a tablet of 10 mg/day, increased after a month to 20 mg and then to 40 mg/die. The mean dosage was 26.25 mg at the 3rd month and 21.25 mg at the 6th. Long-term simvastatin treatment was well tolerated (lack of important side effects as well as of significant changes of other clinical and laboratory parameters) and effective, reducing significantly (p less than 0.01) TC (317.9 +/- 30.8 vs 238.5 +/- 37.9 mg/dl), LDLc (210.6 +/- 48 vs 147.9 +/- 52 mg/dl), ApoB (144.7 +/- 17.5 vs 104.5 +/- 18), and TG (272.9 +/- 184 vs 200.5 +/- 117.6 mg/dl) and increasing in contrast HDL and ApoA values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of a long-term treatment with simvastatin, an inhibitor of HMG-CoA reductase, in dyslipidemic patients at high risk]. 263 79

The relationship between serologic predictors of coronary risk and anthropometric as well as lifestyle characteristics was investigated in 61 men (37.5 +/- 8.5 yrs) and 33 women (40.1 +/- 9.0 yrs). All subjects were healthy non-smokers, mostly middle-class bank employees. In bivariate analysis, among both genders the ratio of waist-to-hip circumference (WHR) was the single best predictor of levels of serum LDL-cholesterol, apolipoprotein B, VLDL-cholesterol and triglycerides (positive association) as well as HDL-cholesterol and apolipoprotein A-I (inverse association). In men, body fat as estimated from bioelectrical impedance measurement was the second best predictor of lipoprotein and apoprotein concentrations, whereas in women it was the body mass index (BMI). The additional independent predictive power of WHR and body fat for the lipid profile was tested in multivariate analysis by adding WHR and body fat sequentially to regression models containing already BMI, endurance capacity, exercise, alcohol consumption and age. For example, explained variance of triglyceride distribution rose from 26.3 to 35.1% (P = 0.01 for increase) when body fat was entered into the regression equation, or inclusion of WHR into a model already containing age, the behavioral variables, BMI, and body fat increased the explained variance of LDL/HDL-cholesterol ratio from 20.9 to 27.6% (P = 0.04 for increase). In women, the same regression models were even slightly more predictive for the serum lipid profile. Endurance capacity was related to a low atherogenic risk lipid profile in bivariate analysis but lost much of its predictive power in multivariate analysis, which confirms that the effect of fitness on lipid levels is probably mediated in part by a low body fat content. It is concluded from this cross-sectional investigation that studies which focus on associations between lifestyle and serologic predictors of atherogenic risk should possibly include the WHR and a measure of body fat, since the latter two appear to be closer correlates of serum lipoprotein and apolipoprotein levels than BMI or single behavioral factors, at least among male non-smokers.
Atherosclerosis 1989 Feb
PMID:Anthropometric and lifestyle correlates of serum lipoprotein and apolipoprotein levels among normal non-smoking men and women. 271 56


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