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)

Fifteen non-obese patients with familial hypercholesterolemia and fifteen normocholesterolemic subjects matched for age, body mass index, waist/hip ratio, arterial blood pressure and sedentary life style underwent blood sampling for determination of fasting plasma glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides, free fatty acids, apolipoprotein A1 and B. In both groups of subjects we determined erythrocyte membrane microviscosity and performed an echocardiographic study. We demonstrated that hypercholesterolemic patients had a significant increase in fasting plasma total cholesterol (8.9 +/- 0.5 vs. 5.5 +/- 0.3 mmol/l, P less than 0.001), insulin (79 +/- 4 vs. 58 +/- 4 pmol/l, P less than 0.05) and apolipoprotein B (2.2 +/- 0.5 vs. 1.3 +/- 0.5 g/l P less than 0.01). In the echocardiographic study we found a significant impairment in left ventricular relaxation (isovolumic relaxation time (IRT) 106 +/- 6 vs. 73 +/- 7 ms, P less than 0.01). Erythrocyte membrane microviscosity (0.253 +/- 0.004 vs. 0.225 +/- 0.003, P less than 0.05) was also increased in hypercholesterolemic patients. Finally we found that erythrocyte membrane microviscosity correlated with fasting plasma insulin levels (r = -0.46, P less than 0.03) and IRT (r = -0.52, P less than 0.01).
Atherosclerosis 1992 Sep
PMID:Impaired left ventricular relaxation and hyperinsulinemia in patients with primary hypercholesterolemia. 141 3

The St. Thomas Hospital (STH) rabbit has been previously shown to have a Mendelian form of hypertriglyceridemia, accompanied by accelerated atherosclerosis, and these animals may serve as a useful model for human dyslipoproteinemia syndromes. Here we describe the establishment of a new colony of these STH animals, and present genetic analysis of triglyceride (TG) and apolipoprotein B (apoB) levels. Segregation analysis of TG in 39 STH animals and 24 controls gave evidence of Mendelian segregation for an allele leading to both elevated TG levels and increased variability in these levels. Predicted means from the most parsimonious model for the Johns Hopkins STH colony were quite similar to that seen in the original London colony, and this model accounted for 80% of the variation in TG seen in the sample. This hypertriglyceridemia locus indirectly influenced the mean apoB levels in these rabbits, and segregation analysis of mean apoB levels suggested a second locus controlling apoB levels. Analysis of residual apoB levels (adjusted for predicted effects of the hypertriglyceridemia locus) revealed clearer evidence for a second locus controlling mean apoB levels in this colony. Arguments for two distinct genetic mechanisms operating in these STH animals are presented.
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PMID:A genetic model for control of hypertriglyceridemia and apolipoprotein B levels in the Johns Hopkins colony of St. Thomas Hospital rabbits. 145 30

Controlled comparisons of the effects of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) as a part of lipid-lowering diets in persons with hyperlipoproteinaemia are sparse. The present study was carried out at a metabolic ward. Forty hyperlipidaemic patients (25 hypercholesterolaemic and 15 hypertriglyceridaemic) were given a 3-week diet rich in either MUFA (saturated fatty acids 7.3 energy% (E%), MUFA 14.6 E%, PUFA 4.8 E%) or PUFA (saturated fatty acids 7.8 E%, MUFA 8.4 E%, PUFA 10.4 E%), but otherwise with an identical composition. The mean serum cholesterol reduction on the MUFA diet was 12% (P < 0.001), with a low density lipoprotein cholesterol reduction of 11% (P < 0.001). The corresponding reductions on the PUFA diet were 15% (P < 0.001) and 16% (P < 0.001). The serum apolipoprotein B and A-I concentrations decreased highly significantly by 13% and 11% on the MUFA diet and by 14% and 11% on the PUFA diet. None of these changes differed between the two diets. Neither were there any differences between the diets regarding the effects on blood glucose, serum insulin and plasma fibrinogen, but there was a significant decrease in serum insulin with a significant reduction of the insulin/glucose ratio after the MUFA diet. The results of this study indicate that MUFA and PUFA are interchangeable within the given frames in lipid lowering diets even in patients with hyperlipidaemia.
Atherosclerosis 1992 Oct
PMID:Effects of lipid-lowering diets enriched with monounsaturated and polyunsaturated fatty acids on serum lipoprotein composition in patients with hyperlipoproteinaemia. 146 45

Familial defective apolipoprotein B-100 is a recently identified, dominantly inherited genetic disorder caused by a G to A mutation in exon 26 of the apolipoprotein B gene. This creates a substitution of glutamine for arginine in the codon for amino acid 3500 and results in reduced affinity of low density lipoprotein (LDL) to the LDL receptor. We have integrated already published data with hitherto unpublished data from 8 countries and a total of 135 affected individuals from 56 families, in an attempt to focus on the range of expression of this mutation on lipid and lipoprotein levels and on coronary artery disease. The frequency of this mutation may be as high as 1 in 500 to 1 in 700 in Europe and in North America. The vast majority of affected heterozygotes have total and LDL cholesterol levels well above the 95th centile for age and gender; in contrast, high density lipoprotein cholesterol, very low density lipoprotein cholesterol and plasma triglycerides are not affected by the mutation. The risk of premature coronary artery disease in the carriers of the mutation is increased to levels as high as those seen in patients with clinical familial hypercholesterolemia; at age 50, about 40% of males and 20% of females heterozygous for the mutation have developed coronary artery disease. Familial defective apolipoprotein B-100 is thus a significant cause of hypercholesterolemia and premature coronary artery disease in Western societies.
Atherosclerosis 1992 Oct
PMID:Familial defective apolipoprotein B-100: a single mutation that causes hypercholesterolemia and premature coronary artery disease. 146 57

The structural and compositional changes occurring during in vitro chemical modification of apolipoprotein B-100 (apo B), the apolipoprotein component of low density lipoproteins (LDL), were investigated in this study. The functional properties of chemically modified apo B and especially its potential to induce accumulation of cholesterol esters in macrophages were related to the structural changes of apo B. Acetylation, maleylation or malondialdehyde conjugation did not significantly affect the lipid composition of LDL. However, the unsaturated cholesteryl esters content, especially that of cholesteryl arachidonate was significantly decreased through Cu-oxidation. The number of reactive lysine residues in apo B was decreased by Cu-catalyzed LDL oxidation, acetylation, maleylation and by malondialdehyde conjugation. The number of free cysteines decreased from six in native apo B-100 to three in Cu-oxidized LDL. The tryptophan fluorescence intensity decreased most in malondialdehyde-conjugated LDL and in Cu-oxidized LDL, compared with acetylated and maleylated LDL. The secondary structure of native and chemically modified LDL was measured by attenuated total reflection infrared spectroscopy and by circular dichroism. No significant changes were observed in the secondary structure of any of the modified LDL. These data suggest that neither acetylation, malondialdehyde treatment or even Cu-oxidation substantially altered the secondary structure of apo B, in spite of significant modifications in the primary structure. Incubation of chemically modified LDL with J774 macrophages induced an accumulation of cellular cholesteryl esters and foam cell formation. The highest cholesterol accumulation was induced after malondialdehyde treatment of LDL. These data suggest that the cellular uptake and accumulation of modified LDL is not modulated by changes in the apo B structure. Rather it seems dependent upon the net charge of the apo B protein and probably involves the modification of critical lysine residues.
Atherosclerosis 1992 Dec
PMID:Structural and functional properties of apolipoprotein B in chemically modified low density lipoproteins. 146 63

The relationship between lifestyle and coronary risk factors in blood was investigated in 165 middle-aged men. Plasma fibrinogen, serum triacylglycerols (TG), and apolipoprotein B (apo B) were higher, and high density lipoprotein cholesterol (HDLc) lower in smokers (n = 69) than in non-smokers (n = 96). By linear regression analysis there was a significant positive association between degree of smoking and either total cholesterol (TC), apo B, or plasma fibrinogen, whereas smoking was inversely related to HDLc. Smoking and coffee intake were positively correlated with an atherogenic index, reflecting the balance between low and high density lipoproteins. Sedentary men (n = 59) had higher mean TC, apo B, and atherogenic index than physically active men (n = 104). Smokers used salt more often than non-smokers. Physically active men used vegetables more often than sedentary men. Combining several habits into a "bad habit" score gave a high level of significance for its association with TC, apo B, and the atherogenic index. The results indicate that lifestyle may influence several blood factors involved in atherosclerosis development.
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PMID:Coronary risk factors in middle-aged men as related to smoking, coffee intake and physical activity. 147 45

Twelve unrelated subjects with heterozygous familial defective apolipoprotein B-100 were identified in a group of 252 patients with type IIa hypercholesterolaemia. Approximately 5% of hypercholesterolaemia can be explained by this mutation in the collective studied. Familial defective apolipoprotein B-100 is therefore the most common known mutation causing primary hypercholesterolaemia. Family studies revealed an additional 14 affected subjects. All family members with the mutation had elevated cholesterol concentrations. In a normolipidaemic control group of 146 subjects the mutation was not present. In the affected individuals a variable expression of total cholesterol concentrations and atherosclerosis was observed. Plasma cholesterol ranged from 6.60 to 14.89 mmol/l with a mean of 9.43 mmol/l. Premature atherosclerosis was present in 4 patients, while one affected woman is now 92 years old and has no symptoms of coronary heart disease or peripheral atherosclerosis. Analysis of the haplotypes and genotypes by 3 biallelic and 1 multi-allelic DNA marker suggests that the disorder is caused in all affected patients by the same rare allele. The fact that the same mutant allele was also identified in other European populations and in a North American population of Caucasian origin argues for a common European origin of this mutation.
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PMID:Familial defective apolipoprotein B-100 in 12 subjects and their kindred. 148 44

Forty-three patients with clinically and biochemically unequivocally defined type III hyperlipoproteinemia (HLP) were screened for the presence of the apolipoprotein (apo) B-100 arginine3500-->glutamine mutation. This receptor-binding defective apolipoprotein B variant is the cause of familial defective apo B-100 (FDB), an autosomal dominantly inherited disease, which leads to increased plasma cholesterol levels and premature atherosclerosis. Neither patient expressed FDB. It is concluded that the gene defect responsible for FDB is not involved in the pathogenesis of type III HLP.
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PMID:Screening for the apolipoprotein B-100 arginine3500-->glutamine mutation in patients with type III hyperlipoproteinemia. 149 42

Lipoprotein(a) (Lp[a]), a highly atherogenic lipoprotein particle, is the prominent apolipoprotein B-containing lipoprotein in the hedgehog (Laplaud PM et al, J Lipid Res 1988;29:1157-1170). In the present work, we studied the consequences of the structural homology between the specific Lp(a) glycoprotein, apoprotein(a), and plasminogen on the generation of plasmin by fibrin-bound tissue-type plasminogen activator. The activation of plasminogen was initiated by adding either native plasma or Lp(a)-free plasma supplemented with the equivalent of 0.25 mg/ml of either purified Lp(a) or albumin to a surface of fibrin prepared on micortitration plates and to which human tissue-type plasminogen activator was specifically bound. With the Lp(a)-free plasma, an increase in the binding and activation of plasminogen as a function of time was observed. In contrast, in the presence of Lp(a) (i.e., native plasma or the reconstituted system), a significant decrease in the binding of plasmin(ogen) (approximately 60%) was obtained. These data indicate that hedgehog Lp(a) interferes with the binding and activation of plasminogen at the fibrin surface and may thereby behave as a factor regulating the extent of fibrin deposition. These results support our previous data indicating that high levels of Lp(a) may have antifibrinolytic effects in humans (Rouy D et al, Arterioscler Thromb 1991;11:629-638), are in agreement with the observation that Lp(a) is a risk factor for atherosclerotic disease, and provide further support to the view of Lp(a) as a link between atherosclerosis and thrombosis.
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PMID:Hedgehog lipoprotein(a) is a modulator of activation of plasminogen at the fibrin surface. An in vitro study. 153 29

Serum lipoprotein (a) (Lp[a]) has been associated with coronary artery atherosclerosis. Its association with restenosis after percutaneous transluminal coronary angioplasty (PTCA) has not been previously studied. Serum levels of Lp(a), in addition to other lipoproteins, and their components using standard assays, were determined in subjects undergoing cardiac catheterization within 10 months after PTCA. Clinical (e.g., sex, diabetes, angina class) and angiographic (e.g., PTCA percent diameter reduction) factors were not different between the group without (diameter reduction less than 50%; group A) and the group with (diameter reduction greater than or equal to 50%; Group B) restenosis. Total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol, apolipoprotein A-I, apolipoprotein B and Lp(a) were compared. Univariate predictors of restenosis were serum triglycerides (2.50 +/- 1.07 mmol/liter for group A vs 1.72 +/- 0.79 +/- mmol/litre for group B, p = 0.008), and Lp(a) (median: 7.0 mg/dl [range 0 to 44] for group A vs 19 mg/dl [range 1 to 120] for group B; p = 0.006). Stepwise logistic regression revealed the only significant independent predictor of restenosis to be serum Lp(a) (p = 0.018). Each quintile of Lp(a) was associated with a progressively higher risk of restenosis, with the highest quintile (40 to 120 mg/dl) having an odds ratio of 11 (95% confidence interval 9 to 13) compared with the lowest quintile (0 to 3.9 mg/dl) (p = 0.033). A serum Lp(a) of greater than 19 mg/dl was associated with an odds ratio of 5.9 (95% confidence interval 4.6 to 7.2) (restenosis rates of 58% in the group with 0 to 19 mg/dl and 89% in the group with 19 to 120 mg/dl; p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Usefulness of serum lipoprotein (a) as a predictor of restenosis after percutaneous transluminal coronary angioplasty. 144 34


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