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)

Familial combined hyperlipidemia (FCHL) appears to be the most common, simply inherited hyperlipidemia strongly associated with coronary heart disease. In the family examined in this study, two of the siblings who met diagnostic criteria for FCHL had extensive clinical atherosclerosis before age 30, unusually premature for this form of hyperlipidemia. Lipoproteins and low-density lipoprotein (LDL) apolipoprotein (apo) B metabolism were characterized in these siblings in an attempt to gain insight into the cause of the rapid atherosclerosis in the two siblings so affected. LDL apo B production rates were very high in all three siblings (25 to 30 mg/kg/d), consistent with FCHL. beta-Very-low-density lipoprotein-beta (beta-VLDL) was present in the plasma of both siblings with accelerated atherosclerosis. The isoapolipoprotein E pattern in both of these siblings was E-3/E-2. In the third sibling, who was free of premature clinical atherosclerosis and lacked plasma beta-VLDL, the pattern was E-3/E-3. Thus, the heterozygote apo E-3/E-2 pattern may be related to the accumulation of beta-VLDL in persons with a very high apo B production rate. The abnormal accumulation of beta-VLDL may be one of the possible explanations for the rapid, premature atherosclerosis in the two siblings with FCHL in this kindred. Both male members in this kindred also had low levels of high-density lipoproteins, and thus may have had an additional risk of developing atherosclerosis due to this lipoprotein abnormality as well.
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PMID:Metabolism of apolipoprotein B in members of a family with accelerated atherosclerosis: influence of apolipoprotein E-3/E-2 pattern. 154 61

We analyzed serum lipoproteins and apolipoprotein E (apo E) from 199 patients in CCU, having ischemic heart disease, and from 211 healthy subjects. It was suggested that serum lipoprotein abnormalities, especially elevated low density lipoprotein (LDL) levels, are closely related to atherogenesis in relatively young patients and subjects with severe coronary lesions. The frequency of apo E-4 was higher and that of E-2 was lower in the CCU group than in the control group. Apo E mutants, E-7 (Glu244----Lys, Glu245----Lys) and E-5 (Glu3 (Glu3----Lys), were also frequent in the CCU group. Apo E isoproteins have higher pI in the order E-2, E-3, E-4, and we observed that LDL-cholesterol levels increased in the same order. The apo E mutants, E-5 and E-7, are also more basic than E-4. These findings suggest that basic apo Es were associated with the development of atherosclerosis. The prevalence of familial hypercholesterolemia (FH) in the CCU group was more than 10 times higher than the reported frequency of FH heterozygotes in normal population. The persistence of marked hypercholesterolemia from infancy probably makes FH patients susceptible to atherosclerosis. Based on the analysis of LDL-receptor protein synthesis, various types of mutations were observed even in phenotypically homozygous FH patients. FH homozygotes were divided into 2 groups, a receptor-negative group and a receptor-defective group. We found a great difference in the frequency of coronary heart disease depending on whether even a small number of receptors were present or not.
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PMID:Hyperlipoproteinemia as a risk factor for ischemic heart disease. 239 26

The human hepatoma cell line, Hep G2, has been used to compare the metabolism by isolated liver cells of purified isoforms of human apolipoprotein E (apo E). Complexes of [125I]apo E-3/3, 2/2, 3/2 and 4/3 with dimyristoyl phosphatidylcholine (DMPC) were prepared by a detergent-dialysis method: discoidal, bilayer complexes with a stoichiometry of 125 +/- 15 mol DMPC/mol apo E resulted. The predominant phenotype apo E-3/3, and the phenotype apo E-2/2 characteristic of patients with Type III hyperlipoproteinemia, interact similarly with DMPC and adopt the same conformation with 60-70% alpha-helix, as monitored by circular dichroism spectroscopy. The uptake and degradation at 37 degrees C, and binding at 4 degrees C by Hep G2 cells, of [125I]apo E-3/3/DMPC and [125I]apo E-2/2/DMPC complexes were compared. Apo E-3/3 was degraded more rapidly than apo E-2/2 suggesting that the diminished catabolism of the latter phenotype by intact livers is due to lack of recognition by the hepatocytes. The observed degradation of apo E was 3-4 times greater than that which could be attributed to fluid phase endocytosis and low-affinity adsorptive endocytosis. The degradation of [125I]apo A-I by Hep G2 cells can be accounted for by the above endocytotic mechanisms. The distinction between apo E-3/3 and apo E-2/2 isoforms is attributed to the presence of a cell-surface receptor on Hep G2 cells which binds apo E-3/3 with a higher affinity than apo E-2/2.
Atherosclerosis 1984 Aug
PMID:The conformation of apolipoprotein E isoforms in phospholipid complexes and their interaction with human Hep G2 cells. 608 44

We analyzed the heterogeneity of apo E in very low density lipoprotein from 58 hyperlipidemic subjects with or without atherosclerosis, 69 patients with ischemic heart disease, and 100 apparently healthy individuals. Apo E gene frequencies in the group of healthy individuals were comparable with those in German and American populations. The distribution of six common apo E phenotypes in the groups of hyperlipidemia and ischemic heart disease was similar to that in the healthy group. In addition to the three major isoforms of apolipoprotein E (apo E-4, E-3, and E-2) and the new one (apo E-5) which was recently found in this laboratory, we have discovered an additional series of components, which showed themselves as at least three bands on an isoelectric focusing gel in the region of E-VII through E-V, in four patients with hyperlipidemia and atherosclerosis. The new series of apo E components, named apo E-Suita, was identical with the ordinary apo E in its interaction with heparin-Sepharose gel and with anti-apo E antibody. The most basic component of apo E-Suita (E-VII) was the unsialylated form and other components (E-VI and E-V), the sialylated forms. Family studies revealed that apo E-Suita was determined by inheritance of a new apo E allele located at the same locus as the hitherto known apo E components. Apo E-5 and apo E-Suita isoproteins had isoelectric points more basic than apo E-3, the parent type, by two and four units of charge, respectively. While the apo E-Suita isoprotein had the same molecular weight as ordinary major apo E isoproteins, the molecular weight of the apo E-5 isoprotein was approximately 1,500-2,000 lower than the other apo E isoproteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The incidence of abnormal apo E components, including apo E-5 and apo E-Suita, was high among patients with hyperlipidemia and ischemic heart disease (7:127), while we could not find such components among 100 healthy individuals. Moreover, five of seven patients with the abnormal apo E had overt atherosclerotic disease. The findings suggest that these kinds of apolipoprotein mutation are closely related to the development of atherosclerosis.
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PMID:New mutants of apolipoprotein E associated with atherosclerotic diseases but not to type III hyperlipoproteinemia. 648 Aug 26

The frequencies of genetic apo E isoforms E2, E3 and E4 were determined in 523 patients with myocardial infarction and compared to those in a control group (1031 blood donors). A significant difference in the frequency of apo E4 was noted between patients and controls (0.05 greater than P greater than 0.025). No differences in the frequencies of isoforms E3 and E2 were observed. In particular, there was no significant difference between the two groups in the frequency of apo E2 homozygosity, a condition that is associated with type III hyperlipoproteinemia. However, all E2 homozygote survivors of myocardial infarction had hyperlipoproteinemia type III (cholesterol 269 +/- 29 mg/dl; triglyceride 419 +/- 150 mg/dl; age 54 +/- 14 years; N = 5). On the contrary, E2 homozygote controls (all apo E-2/2 blood donors and their apo E-2/2 relatives who were from the same age range as the patients) had primary dysbetalipoproteinemia but normal or subnormal plasma cholesterol concentrations (cholesterol 184 +/- 28 mg/dl; triglyceride 151 +/- 52 mg/dl; age 56 +/- 13 years; N = 11). This indicates that E2 homozygotes with hyperlipoproteinemia type III who occur rarely in the population but comprise about 1% of myocardial infarction patients have a markedly increased risk for coronary atherosclerosis, whereas the risk for E2 homozygotes with normal or subnormal plasma cholesterol (= primary dysbetalipoproteinemia) may be considerably lower than for the general population. The data illustrate the complex relationship between apo E genes, lipid levels, and risk for atherosclerosis.
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PMID:Apolipoprotein E phenotypes in patients with myocardial infarction. 669 48

Heterogeneity of apolipoprotein E (apo E) was analyzed by isoelectric focusing of apo VLDL in patients with hyperlipidemia and/or atherosclerosis. Six major apo E phenotypes were shown, in agreement with the current genetic model which is composed of 3 major apo E isoproteins, apo E-4, apo E-3 and apo E-2, resulting from three apo E alleles, epsilon 4, epsilon 3 and epsilon 2, at a single genetic locus. We recognized an additional apolipoprotein band, which is located basic to apo E-4 on an isoelectric focusing gel, in 3 patients with hyperlipidemia. The new apolipoprotein component, named apo E-5, was identical with ordinary apo E in apparent molecular weight by SDS-polyacrylamide gel electrophoresis and in its interactions with heparin-Sepharose gel and with anti-apo E antibody. This mutant apo E isoprotein had an isoelectric point more basic by one unit of charge than apo E-4. Two of 3 patients had the phenotype E5/3, and the other the phenotype E5/4. Genetic analysis of the apo E phenotypes in family members of the patients indicated the presence of a new apo E allele (epsilon 5) at the same genetic locus as hitherto known alleles. Since most of the subjects above 50 years old with apo E-5 had ischemic heart disease or cerebral infarction, it was suggested that the mutant apo E-5 may possibly be related to the development of atherosclerosis.
Atherosclerosis 1984 Feb
PMID:A new isoform of apolipoprotein E--apo E-5--associated with hyperlipidemia and atherosclerosis. 671 69

The current study compared the acute effect of human apolipoprotein (apo) E isoforms on plasma lipids, lipoproteins and apolipoproteins 6 h after a bolus intravenous injection of individual isoforms into apo E-deficient mice. We found a large accumulation of remnant particles not only in the d<1.019 g/ml fraction but also in the d = 1.019-1.063 mg/dl fraction in the setting of absence of endogenous mouse apo E. A significant reduction in total cholesterol (49, 47 and 18%) (P<0.005), cholesterol in the d<1.019 g/ml fraction (56, 50 and 18%) and in the d = 1.019-1.063 mg/dl fraction (38, 40 and 17%) was obtained with apo E-3, E-4 and E-2, respectively. Apo E-3 and E-4 showed more pronounced total cholesterol lowering effect than E-2 (P<0.0001). In the d<1.019 g/ml fraction, apo E-3 and E-4 resulted in a marked decrease in apo B-100 (36 and 34%), B-48 (48 and 52%), A-I (48 and 44%) and A-IV (52 and 46%), respectively. The decrease caused by apo E-2 in apo B-100 (19%), B-48 (16%), A-I (18%) and A-IV (33%) was less than that of E-3 or E-4. In the d = 1.019-1.063 g/ml fraction, an apparent decline in apo B-48 (42 and 38%), A-I (39 and 40%) and an increase in apo B-100 (25 and 18%) were observed after apo E-3 and E-4 injection, respectively, while apo E-2 did not cause an appreciable change in these apolipoproteins (-4 to 6%). Compared to normal saline, liver total cholesterol content was increased by 37, 34 and 16% (P<0.05) after apo E-3, E-4 and E-2 injection, respectively. Apo E-3 and E-4 showed the same high affinity binding to mice hepatic LDL receptor, while apo E-2 was severely defective in binding. These findings indicate that apo E polymorphism is an important factor modulating remnant lipoprotein metabolism.
Atherosclerosis 1998 Dec
PMID:Effect of human apolipoprotein E isoforms on plasma lipids, lipoproteins and apolipoproteins in apolipoprotein E-deficient mice. 986 77

Atherosclerotic narrowing of the renal arteries may result in severe consequences including chronic renal ischemia, renal artery atheroembolism and renal vascular hypertension. Ischemic renal disease is increasingly recognised as a potentially treatable cause of chronic renal failure. Its precise prevalence is still poorly determined as there is no population based studies. The patients with ARD, particularly those with high grade stenosis and systolic hypertension are at very high risk for renal atrophy and renal failure. Angiogram is usually required to confirm the diagnosis. However, the diagnosis is likely in the elderly patient with systemic atherosclerosis and hypertension in whom a rapid rise in serum creatinine concentration is associated with decreased renal length. Disease is associated with high mortality when treated medically. In contrast, clinical improvement is reported after renal revascularisation. Therefore, consider the diagnosis in the patients at risk, because revascularisation (surgical or endovascular) can successfully preserve renal function in selected patients.
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PMID:Ischemic nephropathy. 1086 22