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)

Hypercholesterolemia is commonly associated with primary biliary cirrhosis. In the general population, elevated serum cholesterol is associated with an increased risk of atherosclerosis. The relative risk has been poorly defined in primary biliary cirrhosis patients with hyperlipidemia. In addition, the hyperlipidemic state seen with primary biliary cirrhosis has not been well studied. We prospectively observed 312 patients with primary biliary cirrhosis for a median of 7.4 yr. During this period, 128 patients died. The incidence of atherosclerotic death in patients with primary biliary cirrhosis was not statistically different when compared with an age-matched and sex-matched U.S. control population. A similar group of 50 consecutive PBC patients had detailed serum lipid profiles. Findings included progressive increases in total cholesterol and low-density lipoprotein cholesterol with an increasing histological stage or severity of disease. High-density lipoprotein cholesterol was elevated in all stages, with the highest levels in histological stage 2 and 3 disease. Triglycerides were normal or slightly elevated in all stages. Apoprotein A-I was elevated in all but histological stage 4 disease. Our study suggests the hyperlipidemia associated with primary biliary cirrhosis does not place these patients at risk for atherosclerotic death. In light of the limitations imposed by our relatively small sample size, however, additional patients should be studied. Furthermore, an examination of the pathophysiological mechanisms leading to hypercholesterolemia should be the topic of further study.
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PMID:Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk? 156 27

A spontaneous high density lipoprotein (HDL) deficiency syndrome in chickens associated with a Z-linked (sex-linked) mutation has been reported (F. Poernama et al, J Lipid Res 1990;31:955-963). The mutant, called WHAM (Wisconsin hypo-alpha mutant), has a 70-90% reduction in plasma HDL cholesterol and apolipoprotein A-I (apo A-I) concentrations. In the present study, the effect of the HDL deficiency on diet-induced or spontaneous atherosclerosis was assessed. Control chickens maintained on a high-cholesterol diet for 28 weeks experienced a 2.4-fold rise in the plasma very low density lipoprotein cholesterol concentration, while the same diet induced a 3.7-fold rise in the low density lipoprotein cholesterol concentration in WHAM chickens. The high-cholesterol diet did not elevate the plasma HDL cholesterol or apo A-I concentrations in either group. Both the aortic area of involvement and the width of lesions were quantified by gross and microscopic examination, respectively. Cholesterol feeding produced a significant increase in the area of the aorta with atherosclerotic lesions in both control and mutant chickens. The HDL deficiency in WHAM chickens did not correlate with a higher lesion area or increased lesion thickness. To assess the effect of HDL deficiency on spontaneous atherosclerosis, a separate group of control and WHAM chickens was maintained on a low-fat, cholesterol-free diet for 3 years. At the end of the 3-year period, the area and thickness of the spontaneous aortic lesions in control and WHAM chickens were not significantly different. Spontaneous HDL deficiency in chickens is therefore not associated with increased susceptibility to atherosclerosis.
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PMID:High density lipoprotein deficiency syndrome in chickens is not associated with an increased susceptibility to atherosclerosis. 157 21

The present study evaluated indomethacin therapy--a nonsteroidal anti-inflammatory drug--on experimental hyperlipidemia and atherosclerosis in Rhesus monkeys. Twenty-four monkeys were divided randomly into four groups of six. Two groups received stock pellet diet and two were given an atherogenic diet for six months. After this period, one stock diet-fed group and one atherogenic diet-fed group were treated with oral indomethacin (2.5 mg) on alternate days for a further six months. Serum lipids and lipoproteins were markedly elevated in atherogenic diet-fed monkeys. Generally, indomethacin did not exert a hypocholesterolemic effect; however, liver cholesterol was decreased (P less than 0.05) in atherogenic diet-fed monkeys treated with indomethacin. High density lipoprotein cholesterol was increased in stock diet-fed, indomethacin-treated monkeys but not in atherogenic diet-fed, indomethacin-treated monkeys. Apoprotein A-I was not affected by indomethacin in either stock or atherogenic diet-fed monkeys; however, the drug produced a significant (P less than 0.01) reduction of serum thromboxane B2 in stock diet-fed monkeys, without restoring the 6-keto-prostaglandin F1 alpha to pretreatment levels. A protective role of the drug was noted on both the extent and severity of aortic and coronary atherosclerosis.
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PMID:Effect of indomethacin on serum lipids, lipoproteins, prostaglandins and the extent and severity of atherosclerosis in rhesus monkeys. 157 66

In 16 obese male patients lipid and apolipoprotein A-I and B in serum were assessed before and after weight reduction. The mean age of the subjects was 34.7 +/- 2.7 years, the mean body weight 124.4 +/- 4.0 kg and the mean BMI 39.1 +/- 1.5 kg/m2. After 10 weeks on a low-energy diet of 2500-6000 kJ/day a decline of body weight was observed on average by 14% of the initial value. The total triacylglycerolaemia declined by 46% (p less than 0.02). The total cholesterol level declined by 12% (ns), HDL-cholesterol by 7% (ns), LDL-cholesterol by 8% (ns). The apo A-I did not change during weight reduction, apo B declined by 13% (ns). The ratio of apo B to apo A-I declined by 12.5% (p less than 0.05). The presented results indicate that after weight reduction of obese patients by a low-energy diet the risk of atherosclerosis declines as the apo B/apo A-I ratio declines.
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PMID:[The effect of body weight reduction on apolipoprotein levels in obese patients]. 158 29

Fourteen women and five men participated in a 20-week controlled, cross-over trial of the interaction of simvastatin, an HMGCoA reductase inhibitor, with high and low fat diets. Simvastatin was found to be just as effective at lowering LDL cholesterol whether the subjects were on a 22% fat diet or a 38% fat diet (25% and 29% falls, respectively). Nevertheless, the lowest cholesterol levels were achieved by combining simvastatin with a low fat diet, the latter adding a further 5% reduction in plasma cholesterol. Simvastatin plus a low or high fat diet increased HDL cholesterol by 10.0% and 2.9% respectively (P = 0.003 overall) and reduced triglyceride concentration by 15.9% and 19% respectively (P less than 0.001). Significant diet-drug interactions were seen in LDL and HDL3 cholesterol. Simvastatin blunted the effect of dietary fat change so that the difference in LDL cholesterol, which was 0.71 mmol/l between high and low fat in the absence of simvastatin, was only 0.22 mmol/l with simvastatin. On a high fat diet, simvastatin produced almost no rise in HDL3 cholesterol whereas on a low fat diet HDL3 cholesterol was increased by 8.8% with simvastatin. The cholesterol content of VLDL and LDL were significantly reduced by simvastatin. The effects of diet and drug on apoproteins A-I and B resembles those on HDL and LDL cholesterol. The findings show interactions between simvastatin and dietary fat which have a bearing on the treatment of hypercholesterolemia.
Atherosclerosis 1992 Mar
PMID:Is fat restriction needed with HMGCoA reductase inhibitor treatment? 159 4

Dyslipidemia is a major risk factor for atherosclerosis in adults and children. This study investigated the levels of lipoproteins in a northern Italian pediatric population, in relation to nutritional and familial factors. We studied 650 children on the basis of a 3-day dietary record; 361 of these children had their lipid levels [total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides] measured by a dry, multilayer method and apoprotein A-I and B by an immunonephelometric method. Familial history of cardiovascular disease and dyslipidemia was recorded. Anthropometric variables were taken for each child. Mean TC and low-density lipoprotein cholesterol (LDL-C) were high compared with southern Italian data, but similar to those of other Western countries. Family history of cardiovascular disease could not identify children with higher levels of atherogenic lipoprotein. Nutritional factors affected lipoprotein levels. The most important finding was a higher TC/HDL-C ratio in the lower quartile of polyunsaturated fatty acid intake. Obese children had higher levels of ApoB, triglycerides, TC and LDL-C, and lower levels of HDL-C; figures were higher for obese boys than for obese girls. Our study confirms a high prevalence of elevated levels of atherogenic lipoproteins among the northern Italian pediatric population and an association with nutritional factors and weight.
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PMID:Cholesterol and lipoprotein levels in Milanese children: relation to nutritional and familial factors. 161 95

Recent studies suggest that circulating blood monocytes may serve as a lipid clearance system in early atherosclerotic lesions. To evaluate the influence of moderate hyperlipoproteinemia on monocyte lipid concentrations, we measured fasting serum and monocyte lipid levels in 7 healthy individuals, in 7 patients with primary hypercholesterolemia and in 17 patients with secondary dyslipidemia due to chronic renal failure; 10 of these patients were treated by hemodialysis (HD) and 7 patients by continuous ambulatory peritoneal dialysis (CAPD). The hypercholesterolemic patients had elevated serum levels of total cholesterol, LDL-cholesterol and apolipoprotein (apo) B, but normal plasma triglycerides. Patients on dialysis had elevated serum levels of triglycerides, serum cholesterol (CAPD only) and VLDL- and LDL-cholesterol (CAPD only) and apo B (CAPD only), whereas HDL-cholesterol and apo A-I levels (HD only) were decreased. In monocytes, we measured the content of free cholesterol (FC), cholesteryl esters (CE) and triglycerides (TG). The normal mean intracellular concentrations of FC, CE and TG were 48.3, 1.7 and 2.4 micrograms/mg cell protein, respectively. All monocyte lipid levels were similar in patients and controls, with the exception of a decreased content of FC (30.8 micrograms/mg) in monocytes of HD patients. We conclude that moderate increases in serum lipoprotein lipid levels are not associated with lipid accumulation in monocytes.
Atherosclerosis 1992 Jun
PMID:Lipid levels in monocytes of patients with moderate hyperlipoproteinemia. 163 66

Cholesteryl ester transfer protein may play a role in the cholesteryl ester metabolism between high density lipoproteins (HDL) and apolipoprotein B-containing lipoproteins. To investigate relationship between HDL and cholesteryl ester transfer protein (CETP) activity in the development of atherosclerosis, the present study has focused on CETP activity in the patients with familial hypercholesterolemia (GH). HDL-C and HDL-C/apo A-I mass ratio in heterozygous FH were lower than those in normolipidemic controls. There was a 2-fold increase in total CETP activity in incubated FH serum compared with normolipidemic controls. Assays for CETP activity in the lipoprotein deficient serum (d greater than 1.215 g/ml) were carried out by measuring the transfer of radioactive cholesteryl ester from HDL (1.125 less than d less than 1.21 g/ml) to LDL (1.019 less than d less than 1.060 g/ml). CETP activities in heterozygous FH (79 +/- 4 nmol/ml/h) was significantly higher than those in normolipidemic controls (54 +/- 6 nmol/ml/h). The increased total cholesteryl ester transfer mainly results from increased CETP activity in the d greater than 1.215 g/ml, possibly reflecting an increase in CETP mass in serum. Increased CETP activity in the d greater than 1.215 g/ml was correlated positively with IDL-cholesterol/triglyceride mass ratio (r = 0.496, p less than 0.01), and negatively with HDL-cholesterol/apo A-I mass ratio (r = -0.334, p less than 0.05). These results indicate that the enhanced CETP activities may contribute to increase risk for developing atherosclerosis in FH by changing the distribution of cholesteryl ester in serum lipoproteins.
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PMID:Enhanced cholesteryl ester transfer protein activities and abnormalities of high density lipoproteins in familial hypercholesterolemia. 163 94

Data from various laboratories have indicated associations of various alleles determined by RFLPs within or adjacent to several apolipoprotein genes with abnormalities in plasma lipids and/or premature coronary artery disease (CAD). In order to assess such relationships we have examined allele frequencies of 8 different RFLPs within or adjacent to the apo A-I, C-III and A-IV gene complex on the long arm of chromosome 11 (MspI, 5' to the apo A-I gene; MspI, within the apo A-I gene; PstI, 3' to the apo A-I gene; SstI, 3' to the apo C-III gene; PvuII, within the apo C-III gene; PvuII, 5' to the apo C-III gene; XbaI, within the apo A-IV gene; and XbaI, 3' to the apo A-IV gene) in 202 patients with CAD (50% narrowing of one or more coronary arteries) prior to age 60 and 145 normal controls. None of the allele frequencies of these RFLPs were significantly different in cases as compared to controls. With regard to associations with plasma lipids and apolipoprotein levels, the rare allele determined by the absence of the PstI site was associated with elevated triglyceride levels (P less than 0.05) in cases, but not in controls. In contrast, the rate MspI allele 5' to the apo A-I gene was associated with elevated triglyceride levels (P less than 0.05) in controls but not in cases. In both cases and controls, subjects with the uncommon SstI allele had triglyceride levels that were 9 and 38% higher than in those without this allele. These differences were significant (P less than 0.05) only in controls. Our data indicate that the rare allele determined by the SstI site within this gene complex deserves further study in order to understand its association with elevated triglycerides in Caucasian populations. However, at the present time all these DNA markers lack sufficient specificity to be clinically useful for CAD risk assessment.
Atherosclerosis 1991 Mar
PMID:Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature coronary artery disease. 167 4

Lipoprotein (Lp) cholesterol and apolipoproteins (apo) A-I and B levels have been shown to be better markers for the presence of coronary artery disease than total cholesterol. In this study, we determined the plasma levels of lipoprotein particles containing apo A-I only (LpA-I), apo A-I and A-II (LpA-I:A-II), apo B and C-III (LpB:C-III) and apo B and E (LpB:E) in 145 patients with coronary artery disease (mean age +/- SD, 51 +/- 7 years) and 135 healthy control men (mean age 49 +/- 11 years). Patients with CAD had lower high density lipoprotein (HDL) cholesterol and apo A-I levels and higher triglycerides and apo had lower high density lipoprotein (HDL) cholesterol and apo A-I levels and higher triglycerides and apo B levels than controls. In patients with CAD, LpA-I (0.341 +/- 0.093 vs. 0.461 +/- 148 g/l) and LpA-I:A-II (0.694 +/- 0.171 vs. 0.899 +/- 0.148 g/l) were lower, whereas LpB:E (0.372 +/- 0.204 vs. 0.235 +/- 0.184 g/l) were higher than in controls (cases vs. controls, all P less than 0.005). No significant differences were observed for LpB:C-III (0.098 +/- 0.057 vs. 0.107 +/- 0.061 g/l, p = 0.235) particles. Discriminant analysis indicates that LpA-II:A-I, LpE:B, LpA-I, and triglycerides best differentiate between cases and controls. Plasma apo C-III (0.027 +/- 0.008 vs. 0.036 +/- 0.020 g/l) and E (0.040 +/- 0.015 vs. 0.055 +/- 0.029 g/l) were lower in the CAD group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1991 Oct
PMID:Plasma apolipoprotein A-I, A-II, B, E and C-III containing particles in men with premature coronary artery disease. 168 7


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