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)

Apolipoprotein E (apoE) is a ligand for receptors that clear remnants of chylomicrons and very low density lipoproteins. Lack of apoE is, therefore, expected to cause accumulation in plasma of cholesterol-rich remnants whose prolonged circulation should be atherogenic. ApoE-deficient mice generated by gene targeting were used to test this hypothesis and to make a mouse model for spontaneous atherosclerosis. The mutant mice had five times normal plasma cholesterol, and developed foam cell-rich depositions in their proximal aortas by age 3 months. These spontaneous lesions progressed and caused severe occlusion of the coronary artery ostium by 8 months. The severe yet viable phenotype of the mutants should make them valuable for investigating genetic and environmental factors that modify the atherogenic process.
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PMID:Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. 141 43

Apolipoprotein E phenotypes and gene frequencies were determined in 560 patients receiving long-term hemodialysis. In addition, fasting plasma lipid- and apolipoprotein-concentrations were evaluated in 245 of these individuals. The distribution of the three major apolipoprotein E alleles (epsilon 4, epsilon 3, and epsilon 2) and that of the six common apolipoprotein E phenotypes (E4/4, E3/3, E2/2, E4/2, E4/3, and E3/2) in the dialysis group was nearly identical to that of healthy controls. Patients with the apolipoprotein E phenotypes E2/2, E4/4 and E4/3 (comprising 24% of the whole group) had higher mean plasma cholesterol- and triglyceride-concentrations than those with the apolipoprotein E phenotypes E3/3 and E3/2 (72% of the whole group). Thus, the genetic polymorphism of apolipoprotein E may contribute to the individual risk of accelerated atherosclerosis in patients under maintenance hemodialysis.
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PMID:Apolipoprotein E phenotypes and hyperlipidemia in patients under maintenance hemodialysis. 173 33

A delayed clearance of postprandial lipoproteins from the plasma may play a role in the etiology of premature coronary atherosclerosis. To address this hypothesis, we studied chylomicron (remnant) metabolism in two groups of 20 selected normolipidemic men aged 35-65 years, a group of coronary artery disease (CAD) patients, and a matched control group with documented minimal coronary atherosclerosis. Subjects received an oral fat load supplemented with cholesterol and retinyl palmitate. Plasma samples obtained during the next 24-hour period were analyzed for total as well as d less than 1.019 g/ml and d greater than 1.019 g/ml triacylglycerol, cholesterol, and retinyl ester concentrations. Although both groups of patients responded identically in terms of the appearance of gut-derived lipids in the plasma, CAD patients showed a marked delay in the clearance of retinyl esters as well as in the normalization of plasma triacylglycerol concentrations. Postheparin plasma hepatic lipase activity was significantly lower in the CAD group. Apolipoprotein E phenotype measurements did not reveal marked differences in frequency between both groups. The frequency distribution was not unusual in comparison with the normal Dutch population. The magnitude of the postprandial responses of triacylglycerol and retinyl esters was correlated positively with the fasting levels of plasma triacylglycerol and negatively with high density lipoprotein subfraction 2 cholesterol concentrations. These data indicate that the clearance of postprandial lipoproteins in normolipidemic CAD patients as selected in the present study is delayed as compared with that of controls without coronary atherosclerosis and suggest that postprandial lipoproteins may play a role in the etiology of their disease.
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PMID:Postprandial lipoprotein metabolism in normolipidemic men with and without coronary artery disease. 202 3

Plasma lipids and apolipoproteins were quantified in two kindreds of hypobetalipoproteinemia. All affected members were asymptomatic but showed a decrease of 75% in apolipoprotein B and of 69% in LDL-cholesterol. There were no major changes in apo A-I and A-II but all affected family members had reduced levels of apo C-II (by 58%) and C-III (by 59%) without significant decrease in apo C-I and no specific decrease of apo C-III1. Apolipoprotein E is decreased in SDS-PAGE. The plasma level and phenotype of Lp(a) are not affected by HBL, suggesting that a catabolic rather than a synthetic mechanism is responsible for the disease. As shown by density gradient ultracentrifugation, HDL2 particles that contain essentially apolipoprotein A-I, cholesterol and phospholipids represent in affected subjects the major part of HDL. Due to the net reduction of apolipoprotein B-containing particles (VLDL and LDL) as acceptors of lipids in HBL, there is an accumulation of large particles rich in cholesteryl esters.
Atherosclerosis 1990 Aug
PMID:Plasma lipids, lipoproteins and apolipoproteins in two kindreds of hypobetalipoproteinemia. 224 96

Hypercholesterolemia and atherosclerosis were induced in New Zealand White rabbits by cholesterol feeding. Apolipoprotein E mRNA levels in livers were found to be slightly increased, as determined by Northern blots. Apolipoprotein E gene expression was dramatically induced in rabbit atherosclerotic aortas with respect to healthy aortas. However, apolipoprotein E mRNA levels in atherosclerotic aortas were low as compared with the hepatic mRNA levels of the same animals. Interestingly, we also found a significant increase in apolipoprotein E expression in human atheromata with respect to healthy aorta from the same individual. This is the first report on apo E gene induction in human atherosclerotic lesions.
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PMID:Induction of apolipoprotein E gene expression in human and experimental atherosclerotic lesions. 233 34

Apolipoprotein E (apo E), a component of VLDL, HDL and chylomicron remnants, is inherited at a single genetic locus with 3 common alleles (epsilon 2, epsilon 3 and epsilon 4). epsilon 2 homozygosity is found in 0-2% of healthy populations, but in 75-100% of subjects with type III hyperlipoproteinaemia, in whom an increased prevalence of glucose intolerance has previously been reported. The lipoprotein abnormality associated with diabetes mellitus has features in common with type III hyperlipoproteinaemia and both conditions lead to accelerated atherogenesis with a similar anatomical distribution. We have therefore examined the frequency of apo E genotypes in 120 subjects with insulin-treated diabetes mellitus (ITDM) and 107 healthy controls, and examined the effect of apo E polymorphism on lipoproteins in the diabetic group. As in the general population, the apo E phenotype in ITDM was a significant determinant of the total serum and LDL cholesterol concentrations which were lowest in patients possessing the epsilon 2 allele, intermediate in those homozygous for epsilon 3 and highest in those with an epsilon 4 allele. The observed gene frequencies of epsilon 2 (0.091), epsilon 3 (0.780) and epsilon 4 (0.130) were similar to those of the healthy control group and those in the general population. However, there was an unexpected increase (P less than 0.0002) in epsilon 2 homozygosity of 6.7% compared to a prevalence of 0.8% predicted both from the Hardy-Weinberg equilibrium and the 0.9% prevalence observed in the healthy control group. This suggests either that epsilon 2 homozygosity increases susceptibility to the development of ITDM or that the two conditions are genetically linked.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1989 Feb
PMID:Apolipoprotein E polymorphism and lipoproteins in insulin-treated diabetes mellitus. 271 62

Apolipoprotein E phenotypes were determined on 417 consecutive lipid clinic patients using an isoelectric focussing technique. Of the 15 patients with phenotype E2/2, 13 (3.1%) had type III hyperlipoproteinaemia and 2 obese identical twins had type V. A further 20 patients (4.8%) had similar plasma and lipoprotein lipid levels but were E2 heterozygotes (14 E3/2 and 6 E4/2). They displayed a widened pre-beta-band almost confluent with the beta-band rather than the broad beta-band shown in classical E2/2 type III patients. In view of the similarities between these heterozygotes and the classical homozygous (E2/2) type III patients and their occurrence in the same families we suggest the nomenclature homozygous and heterozygous type III. In a subsequent comparison between 30 E2/2, 22 E3/2 and 8 E4/2 type III individuals the only significant difference in plasma and lipoprotein lipid parameters was a lower VLDL cholesterol to triglyceride ratio of 0.85 in E3/2 patients than that of 1.24 in E2/2 patients (P less than 0.01). Both homozygous and heterozygous patients showed premature ischaemic heart disease and both responded dramatically and similarly to treatment with clofibrate. These observations indicate that apo E phenotyping is worthwhile in all patients with combined hyperlipidaemia and that homozygous and heterozygous type III hyperlipoproteinaemia is not uncommon.
Atherosclerosis 1985 Nov
PMID:Apolipoprotein E phenotypes in hyperlipidaemic patients and their implications for treatment. 386 82

Subjects with type III hyperlipoproteinemia develop premature atherosclerosis and have hyperlipidemia due to an increase in cholesterol-rich very low density lipoproteins (VLDL) of abnormal electrophoretic mobility. Apolipoprotein E is a major protein constituent of VLDL and appears to be important for the hepatic uptake of triglyceride-rich lipoproteins. A new kindred of patients with type III hyperlipoproteinemia is described in which no plasma apolipoprotein E could be detected, consistent with the concept that type III hyperlipoproteinemia may be due to an absence or striking deficiency of apolipoprotein E.
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PMID:Type III hyperlipoproteinemia associated with apolipoprotein E deficiency. 679 20

Apolipoprotein E isomorphs in very low density lipoproteins and apolipoprotein B of low density lipoproteins were measured in the plasma of normolipidemic subjects with xanthelasmas of the eyelids and in appropriate control groups. All patients tested in the experimental group had an apolipoprotein EII to apolipoprotein EIII ratio typical of the heterozygous state for familial dysbetalipoproteinemia, a hyperapobetalipoproteinemia, or both. Some patients had concomitant atherosclerosis. This is the first report of an increased frequency of the apolipoprotein E-ND phenotype in normolipidemic xanthelasma. This condition should not be dismissed as benign; tissue lipid deposition in the absence of hyperlipidemia might be related to the presence of lipoproteins of abnormal composition with an enhanced atherogenic potential.
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PMID:Increased Frequency of Apo E-ND phenotype and hyperapobeta-lipoproteinemia in normolipidemic subjects with xanthelasmas of the eyelids. 705 63

Apolipoprotein E (apoE)-deficient mice develop marked hyperlipidemia as well as atherosclerosis and thus are an excellent animal model for evaluating the potential for gene therapy in human genetic dyslipoproteinemias. Recombinant adenovirus containing either human apoE (rAdv.apoE) or the reporter gene luciferase (rAdv.luc) were generated and infused intravenously in apoE-deficient mice with preinfusion plasma total cholesterol of 644 +/- 149 mg/dl an cholesterol rich VLDL/IDL. After a single infusion of rAdv.apoE, plasma concentrations of human apoE ranging from 1.5 to 650 mg/dl were achieved. Adenovirus-mediated apoE replacement resulted in normalization of the lipid and lipoprotein profile with markedly decreased total cholesterol (103 +/- 18mg/dl), VLDL, IDL, and LDL, as well as increased HDL. Measurement of aortic atherosclerosis 1 mo after adenoviral infusion demonstrated a marked reduction in the mean lesion area of mice infused with rAdv.apoE (58 +/- 8 x 10(3) microns2) when compared with control mice infused with rAdv.luc (161 +/- 10 x 10(3) microns2; P < 0.0001). Thus, apoE expression for 4 wk was sufficient to markedly reduce atherosclerosis, demonstrating the feasibility of gene therapy for correction of genetic hyperlipidemias resulting in atherosclerosis. The combined use of adenovirus vectors and the apoE-deficient mouse represents a new in vivo approach that will permit rapid screening of candidate genes for the prevention of atherosclerosis.
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PMID:Apolipoprotein E deficiency in mice: gene replacement and prevention of atherosclerosis using adenovirus vectors. 765 31


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