Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The significance of a decreased low density lipoprotein cholesterol/apolipoprotein B ratio (LDL-chol/LDL apo B), or protein-enriched LDL, to predict atherosclerosis was studied in 121 males with angiographically defined coronary artery disease (CAD) and compared to 98 male controls, without history or complaints of vascular disease. Controls were selected for similar age, smoking habits and relative body weight characteristics compared to the CAD group. Covariance analysis with adjustment for hyperlipoproteinemia, apoprotein E phenotype, smoking, age and relative body weight revealed that high density lipoprotein (HDL)-cholesterol was the only parameter that differed significantly between both groups. By logistic regression analysis HDL-cholesterol had the highest predictive power for the development of CAD. The LDL-chol/LDL apo B ratio appeared significantly different between controls and CAD patients (3.1 +/- 0.7 vs. 2.9 +/- 0.6 mmol/g, P less than 0.05), indicating a predominance of subjects with protein-enriched LDL in the CAD group. However, within the group of CAD patients with normal LDL-cholesterol levels no clear distinction could be found between patients with normal and increased LDL apo B levels. Furthermore, it appeared that the LDL-chol/LDL apo B ratio correlated significantly with age (p = -0.24), serum triglycerides (p = -0.24), and HDL-cholesterol (p = 0.24). Thus, the LDL-chol/LDL apo B ratio cannot be considered an independent risk factor for CAD. When adjusted for age, smoking habits and relative body weight the significance of protein-enriched LDL as a risk factor for coronary heart disease diminishes, and HDL-cholesterol appears to be the best indicator for CAD.
Atherosclerosis 1989 May
PMID:The relevance of a protein-enriched low density lipoprotein as a risk for coronary heart disease in relation to other known risk factors. 271 63

It is established in the in vitro experiments that subfraction of HDL3 is able of accepting cholesterol from the atherosclerosis-afflicted aorta intima. Apoprotein E has no effect on the acceptance of cholesterol from the intima by HDL3 particles. The role of the protein under its joint incubation with the aorta intima and HDL3 is reduced to the uptake of cholesterol esters from HDL3-particles enriched by cholesterol. It is assumed that apoprotein E under certain metabolic conditions can transfer esterified cholesterol from HDL-particles on other lipoproteins as well as into tissues impoverished in the cholesterol content.
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PMID:[Participation of apolipoprotein E in the transport of cholesterol esters]. 274 12

Four hypertriglyceridemic patients, who had received an equilibrated high calorie diet and no lipid lowering drug for 1 month, were injected intravenously with 125I-apo C-II and 131I-apo C-III labeled homologous lipoproteins. Plasma and urine radioactivity, lipid and apolipoprotein levels were followed at regular intervals for 15 days. At the end of this first kinetic study the patients were advised to adhere for 1 month to a more restricted diet, limited in fat, and were given additionally 300 mg fenofibrate daily. After this treatment, a new kinetic study involving intravenous injection (similar to the first one) was performed. The protocols of both studies were identical. Treatment (diet plus drug) (1) reduced total cholesterol by 26 +/- 8%, triglycerides by 56 +/- 15%, apo C-II by 36 +/- 14%, and apo C-III by 48 +/- 10%; (2) modified the distribution of radioactivity between lipoproteins proportionally to the change in their mass ratio (decrease in VLDL and increase in HDL); (3) changed the kinetics of both apoproteins by rising the fractional removal rate, shortening residence time and decreasing the synthesis rate of both apolipoproteins C-II and C-III. The treatment was, however, unable to reduce the synthesis rate of apo C-III to normal, suggesting a major role of the apoprotein overproduction in the triggering of hypertriglyceridemia.
Atherosclerosis 1989 Jun
PMID:Apolipoproteins C-II and C-III metabolism in hypertriglyceridemic patients. Effect of a drastic triglyceride reduction by combined diet restriction and fenofibrate administration. 275 46

In order to assess the relationship between obesity and serum lipids, a homogenous group of adult men and premenopausal women is assessed for body mass index, body fat distribution reflected by the waist/hip ratio (WHR), serum lipid parameters and apolipoproteins. Body fat distribution is distinguished in an abdominal and gluteal-femoral type using a cut-off point of 1.00 for the ratio of waist-to-hips girth for men. In women the cut-off value is considered as 0.80 but was also evaluated when considered as 0.85. In the next step tertiles for WHR are created to show a graded relationship between WHR and lipoprotein fraction. The results indicate that WHR is an important determinant for most atherosclerosis-related lipids and apoproteins: in both men (P less than 0.05) and women (P less than 0.005) WHR is significantly correlated with apolipoprotein B. Using multiple regression analysis, in women WHR seems to be the most important dependent variable, where body mass index is not significantly contributing to the explained variance. In men, however, besides WHR age is the most significant variable, although age distribution is similar in men and women. Using tertiles of WHR, we show a clear graded relationship with most lipids and lipoproteins; this gives additionally an argument to confirm that in women WHR = 0.80 is the most accurate cut-off value for abdominal obesity. This study demonstrates that both obese men and women with an abdominal fat mass distribution show a lipid and apoprotein profile that is less favorable than that seen in gluteal-femoral obese subjects insofar as the risk of coronary artery disease is concerned.
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PMID:Apolipoprotein concentrations in obese subjects with upper and lower body fat mass distribution. 276 78

Lecithin:cholesterol acyltransferase (LCAT) and lysolecithin acyltransferase (LAT) are two activities carried out by the same plasma enzyme, but require different apoprotein activators. The LCAT reaction takes place primarily on high density lipoproteins (HDL) and is activated by serum albumin, whereas LAT takes place on low density lipoproteins (LDL) and is inhibited by albumin. In nephrotic syndrome (NS), the levels of serum albumin are reduced, whereas the LDL levels are increased, and therefore, the ratio of LAT/LCAT activities should be increased. To test this hypothesis, we estimated the lipid levels and the two enzyme activities in experimental NS induced in rats by the injection of anti-Fx1A antibody (passive Heymann nephritis). As found in other nephrotic conditions, the plasma lipid levels rose progressively as the proteinuria increased and the serum albumin concentration declined. In addition, the ratio of LAT/LCAT activities increased by about fourfold after nine days of induction of nephritis. The LCAT activity correlated positively and the LAT activity negatively with serum albumin levels. The esterified cholesterol correlated positively with LCAT activity in normal rats but negatively in nephrotic animals, indicating that most of the cholesteryl esters in NS may be non-LCAT derived. The free cholesterol/lecithin ratio, a known risk factor for atherosclerosis, increased significantly in nephrotic rats. Furthermore, since the increase in the LAT activity produces more disaturated lecithins, another putative risk factor, the cumulative risk of coronary heart disease may be increased in long-term NS.
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PMID:Plasma lipids and acyltransferase activities in experimental nephrotic syndrome. 277 94

Apolipoprotein B (apoB) is the major protein component of plasma low density lipoproteins (LDL) and, through its binding to the LDL receptor, it plays a prominent role in lipoprotein metabolism and in the development of atherosclerosis. Specially developed computer programs were applied to detect potential internal repeats in the human apoB sequence and homology of some of these repeats with other apolipoproteins. The simultaneous computer alignment of several (repeated) sequences, carried out in an iterative way to generate consensus sequences, showed the presence of repeated amphipathic helical regions and of repeated hydrophobic proline-rich domains. Extensive Monte-Carlo statistics were used to demonstrate the statistical significance of the internal repeats. Both classes of repeats may contribute to the specific lipid-binding characteristics of apoB. Additional homology, detected between apoB and apoE, the other apolipoprotein-ligand of the LDL receptor, further defined the structural requirements for this receptor-ligand interaction. The computer programs developed in this study should also be useful for detecting internal repeats in other proteins.
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PMID:Human apolipoprotein B: analysis of internal repeats and homology with other apolipoproteins. 282 1

The long term efficacy of granulated guar gum, 15-30 g per day, was studied in 23 patients with severe hypercholesterolaemia (serum cholesterol concentration between 8.0 and 14.3 mmol/l). Originally, 29 patients participated in the study. Two patients dropped out because of gastrointestinal side effects, two others were not willing to complete the study without any given reason, and two discontinued the study because of hospitalization. A 1-month placebo period preceded the guar gum treatment, and another 1-month placebo period followed after 50 weeks of active treatment. The serum total cholesterol concentration (mean +/- SEM) was reduced from 10.0 +/- 0.4 mmol/l to 8.2 +/- 0.3 mmol/l (P less than 0.001) after 8 weeks and to 9.0 +/- 0.4 mmol/l (P less than 0.001) after 50 weeks on guar gum. During the second placebo period serum cholesterol returned to the pretreatment level. After 34 weeks of active treatment the serum LDL-cholesterol concentration had fallen by 15% and that of apoprotein B by 14% from the baseline. The changes in lipid and lipoprotein levels were independent of the initial values and the type of hypercholesterolaemia. Serum triglycerides, HDL-cholesterol, body weight and blood pressure showed no significant changes during the trial. Of the study subjects, 20 reached the maximum intended dose of 30 g per day guar gum between 8 and 14 weeks and thereafter 11 subjects continued the dose of 30 g/day while 12 subjects reduced the dose to 15-25 g/day.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1988 Aug
PMID:Long term treatment of severe hypercholesterolaemia with guar gum. 285 Aug 7

25 of a group of 87 White men had Msp 1 restriction site polymorphism within an Alu sequence 3' to the human apo AII gene. Homozygosity for the polymorphism in 8 men was associated with a significant increase in serum apo AII levels (35.4 +/- 1.70 mg/dl, mean +/- SEM) and altered HDL composition, compared with heterozygotes (31.7 +/- 1.29; n = 17) and normal subjects (29.4 +/- 0.64; n = 62). This is the first account of a common variant of an HDL apoprotein gene that affects HDL composition. In view of its association with a high apo AII concentration homozygosity may protect against atherosclerosis.
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PMID:High-density lipoprotein composition is altered by a common DNA polymorphism adjacent to apoprotein AII gene in man. 285 63

Haplotypes of the apoprotein B gene, localised to chromosome 2, were identified using restriction fragment length polymorphisms (RFLPs) for the enzymes XbaI and EcoRI. Four haplotypes were identified at this locus, X1R1 (H1), X1R2 (H2), X2R1 (H3) and X2R2 (H4); where the X1 and X2 alleles were characterised by gene-related fragments of 5.0 and 8.6 kb respectively and the R1 and R2 alleles by fragments of 13.0 and 11.0 kb respectively. Although the polymorphic sites are less than 10 kb apart, they were found to be in linkage equilibrium. The value of the disequilibrium parameter (D) was 0.0042, approximately 7.5% of the theoretical maximum (Dmax = 0.054). No disease association could be demonstrated between either apoB RFLP, or haplotype, and coronary athersclerosis in our population from south-east England. This was in accordance with a study of apoB RFLPs for a population from the West Coast of the United States, but in contrast to a study of an East-Coast population. There are no previous data for the association between apoB haplotypes and coronary atherosclerosis.
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PMID:DNA haplotypes of the human apoprotein B gene in coronary atherosclerosis. 290 6

To investigate if a change in chromatin organization is associated with the increased transcriptional activity of the apoprotein E (apo E) gene, a study was done in hepatic nuclei isolated after birth to identify areas in or flanking the rat apo E gene with increased sensitivity to DNase I. An area of preferential digestion in the 3'-flanking region of the apo E gene was identified in liver nuclei from 3-day-old pups but not in nuclei from fetal livers collected at day 20 of gestation. This hypersensitive area may contain information important for the regulated expression of the rat apo E gene.
Atherosclerosis 1989 Mar
PMID:Change in chromatin organization of the 3'-flanking region of the rat apoprotein E gene in neonatal rats after an increase in transcriptional activity. 292 63


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