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)

A study was made on the clinical and biochemical features of siblings of patients with hyperchylomicronemia and its inherited relationship. It was not a case of the classical type of familial LPL deficiency, but of familial apolipoprotein C-II deficiency. The first patient with apolipoprotein C-II deficiency was reported by Breckenridge et al. and our patients provide the basis for the second report of this new disease. Our observations in this study strongly suggest that familial apolipoprotein C-II deficiency is transmitted by an autosomal recessive mode of inheritance and heterozygotes of this disorder have no abnormalities of plasma lipid and lipoproteins in spite of the reduced plasma apolipoprotein C-II.
Atherosclerosis 1979 Sep
PMID:Familial type I hyperlipoproteinemia caused by apolipoprotein C-II deficiency. 22 29

The effect of CS-514 (eptastatin, Sankyo Co., Tokyo), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was investigated in 47 patients with hypercholesterolemia (WHO type IIa: 27, IIb: 20). Ten or 20 mg of CS-514 was administered daily for 3 months. In both types of patient, total cholesterol and phospholipid levels were significantly reduced by CS-514. The triglyceride, cholesterol and phospholipid content of low density lipoprotein (LDL) and the plasma levels of apolipoprotein B were also decreased in both groups. In contrast, total triglyceride, very low density lipoprotein (VLDL)-triglyceride and apolipoprotein C-II were decreased only in type IIb subjects. Also the levels of high density lipoprotein (HDL)-cholesterol and apolipoproteins A-I and A-II were increased by CS-514 in IIb but not in IIa patients. In both groups, no change occurred in either the cholesterol/triglyceride or phospholipid ratio in any lipoprotein fraction, nor in the ratio of HDL-cholesterol to apolipoprotein A-I or A-II, respectively. Therefore, CS-514 suppresses plasma levels of cholesterol in hypercholesterolemic patients without modifying lipoprotein composition. Moreover, this drug has different effects on the levels of plasma triglyceride and HDL-cholesterol of type IIa and IIb patients.
Atherosclerosis 1988 Jun
PMID:Effects of CS-514 on plasma lipids and lipoprotein composition in hypercholesterolemic subjects. 313 14

Using a simple and rapid one-dimensional isoelectric focusing technique followed by immunoblotting, we have detected genetic polymorphism of human apolipoprotein C-II (APO C-II) in normal unfractionated plasma samples of individuals of black ancestry. Two common autosomal codominantly expressed alleles, designated APO C-II*1 and APO C-II*2, at the APO C-II structural locus have been observed with frequencies of 0.975 and 0.025 in US blacks and 0.943 and 0.049 in Nigerian blacks. In addition, the gene product of a rare allele designated APO C-II*3 was observed in a single Nigerian black. Apart from a single example of an APO C-II 2-1 phenotype in plasma samples from 187 whites, which was electrophoretically identical to the 2-1 phenotype observed in blacks, it appears that APO C-II*2 is a unique black marker of potential importance in anthropogenetic and atherosclerosis studies.
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PMID:Genetic studies of human apolipoproteins. III. Polymorphism of apolipoprotein C-II. 339 66

Alloxan-diabetic cholesterol-fed rabbits exhibiting severe hypertriglyceridemia are protected against atherosclerosis. In such rabbits most of the plasma cholesterol is found in lipoproteins with a diameter of 75 nm or larger. In the present report it is hypothesized, that due to their large sizes, the lipoproteins of the severely hypertriglyceridemic diabetic rabbits are not able to penetrate the endothelial layer of the arteries. Therefore, the macrophages and smooth muscle cells of the intima will only come in contact with relatively small amounts of cholesterol-carrying lipoproteins. Consequently, cellular accumulation of cholesterol, which is a necessary step in the formation of an atherosclerotic lesion, will be retarded. There are certain parallels between hypertriglyceridemic cholesterol-fed alloxan-diabetic rabbits and humans with familial lipoprotein lipase deficiency, familial apolipoprotein C-II deficiency and insulin-dependent diabetes mellitus in the ketoacidotic state. Based on reports about patients with these metabolic disorders, we suggest that cholesterol in very large lipoproteins also in humans is less atherogenic than cholesterol in smaller lipoproteins.
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PMID:Severe hypertriglyceridemia, large lipoproteins and protection against atherosclerosis. 347 72

Incubation of human plasma at 37 degrees C was shown to induce an increase in the electrophoretic mobility of beta-lipoproteins. beta-Lipoproteins were isolated by density gradient ultracentrifugation after such incubation and their composition was analysed. Incubation decreased the content of free cholesterol and increased that of soluble apolipoproteins. The soluble peptides appearing in LDL upon incubation showed 3 major and 2 minor bands upon polyacrylamide disc gel electrophoresis. Two of the major bands corresponded to apolipoprotein C-III-1 and C-III-2 and one of the minor to apolipoprotein C-II. The addition of an inhibitor to lecithin:cholesterol acyltransferase (LCAT) abolished the increase in electrophoretic mobility and to a large extent diminished the other reported effects of incubation. The hypothesis is put forward that during incubation of plasma at 37 degrees C the free cholesterol in the surface of LDL is removed through the action of LCAT, lipid transferases and exchange processes and is replaced in the surface shell by peptides which cause the change in electrophoretic mobility.
Atherosclerosis 1984 Dec
PMID:Increase of electrophoretic mobility and of content of soluble proteins of human plasma beta-lipoproteins by incubation of plasma in vitro. 652 47

Lipoprotein and apolipoprotein concentrations were determined in 11 homozygous and 9 heterozygous subjects for familial apolipoprotein C-II (Apo C-II) deficiency. Apo C-II was not detectable in the homozygotes, with the exception of 1 subject who possessed immunochemically detectable quantities in one of two samples. Apolipoproteins C-III (Apo C-III) and E (Apo E) were elevated 2-3-fold in 9 of 11 homozygotes. Apo C-III, but not Apo E, correlated with triglyceride levels (1500-4100 mg/dl). However, both Apo C-III and Apo E correlated with the cholesterol levels and one another. Apolipoproteins A-I (Apo A-I), A-II (Apo A-II) and B (Apo B) were reduced to approximately 50-60% of normal values in association with very low levels of cholesterol in high density (HDL; 11 +/- 2 mg/dl) and low density (LDL; 19 +/- 6 mg/dl) lipoproteins in the homozygous subjects. These alterations were associated with a marked decrease in the proportion of plasma Apo C-III associated with HDL. The levels of apolipoprotein D (Apo D) were within the normal range. Nine obligate heterozygotes had Apo C-II concentrations (mean 1.8 +/- 0.5 mg/dl; range 1.2-2.7 mg/dl) which were approximately 40-50% of normal values (mean 2.9 +/- 0.9 mg/dl; range 1.7-5.6 mg/dl). The reduction in absolute amounts of Apo C-II was also reflected in a reduction of the ratio Apo C-II/Apo C-III in very low density lipoproteins (VLDL) and in a reduction in the ability of the sera to activate skim milk lipoprotein lipase. The concentrations of Apo A-II, Apo B, Apo C-III and Apo E were normal. Apo A-I concentrations were normal or slightly low in association with slightly reduced concentrations of HDL cholesterol and a low proportion of plasma Apo C-III in HDL in relation to LDL and VLDL in some heterozygotes. It is concluded that the marked alterations in the apolipoprotein levels in homozygous subjects are primarily a reflection of the deficiency of Apo C-II which results in severe hypertriglyceridemia. In heterozygotes, the partial deficiency of Apo C-II appears to result in a minor disturbance of the clearance of the triglycerides and Apo C-III rich particles but no marked changes in the concentrations of total lipids, lipoproteins and apolipoproteins in fasting plasma.
Atherosclerosis 1982 Aug
PMID:Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency. 713 21

The polypeptide composition of a variant lipoprotein (d less than 1.006) carrying a relative excess of apolipoprotein C-II has been characterised by polyacrylamide gel electrophoresis and isoelectric focussing. The apo-C peptides of the variant lipoprotein contained 45.2 +/- 1.3 (n = 9) % of apo C-II compared with 21.5 +/- 5.4 (n = 30) % for hypertriglyceridaemic controls. The variant lipoprotein activated purified bovine milk lipoprotein lipase normally, but was an inefficient substrate for this enzyme as assessed by direct release of fatty acids from the lipoprotein or by a substrate competition assay. Electron microscopy revealed the variant lipoprotein as non-spherical flattened particles compared with the more spherical appearance of control triglyceride-rich lipoproteins. We suggest that the relative proportion of apo C peptides associated with the lipoprotein particle may be critical for optimal enzyme-substrate interaction.
Atherosclerosis
PMID:An abnormal triglyceride-rich lipoprotein carrying excess apolipoprotein C-II. 747 Jan 92

Individuals with elevated levels of plasma cholesterol and triglyceride may be at higher risk for coronary artery disease than those with isolated elevations of either cholesterol or triglyceride. Sequence variation in the A-I/C-III/A-IV gene cluster has been implicated in the etiology of some disorders associated with premature atherosclerosis and/or hypertriglyceridemias with or without elevations of cholesterol. This led to the hypothesis that allelic variation at this gene locus alters plasma lipid transport and affects susceptibility for atherosclerosis. The study population, from the Atherosclerosis Risk in Communities (ARIC) Study, consisted of 50 normolipidemic individuals, 48 subjects with elevated plasma cholesterol, 47 subjects with elevated plasma triglyceride, and 123 subjects with both elevated plasma cholesterol and triglyceride who were used to evaluate associations between an Xmn I polymorphic site 2.5 kilobase pairs (kbp) upstream of the structural gene for apolipoprotein (apo) A-I, intimal-medial thickening of the extracranial carotid arteries, and several plasma lipid factors. The relative allele frequencies of the 8.3-kbp allele and the 6.6-kbp allele were .86 and .14, respectively, in the entire study population and did not differ among the lipid phenotypes. In the group with elevated plasma cholesterol and triglyceride, subjects possessing the 6.6-kbp allele exhibited a greater carotid artery intimal-medial thickness (P = .034) and higher plasma levels of apoA-I, high-density lipoprotein (HDL) cholesterol, and HDL3 cholesterol (P < .02) than subjects homozygous for the 8.3-kbp allele. In contrast, subjects with the 6.6-kbp allele displayed lower mean ratios of apolipoproteins C-II to C-III, C-II to A-IV and E to A-IV in plasma (P < .05) and a lower mean ratio of apolipoprotein C-II to C-III in the triglyceride-rich lipoproteins (P = .026). Sequence variation in or near the genes encoding apolipoproteins A-I, C-III, and A-IV may therefore identify a group of hypercholesterolemic-hypertriglyceridemic persons who are at higher risk for atherosclerosis than others with the same lipoprotein phenotype.
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PMID:Associations of allelic differences at the A-I/C-III/A-IV gene cluster with carotid artery intima-media thickness and plasma lipid transport in hypercholesterolemic-hypertriglyceridemic humans. 819 77

Disorders in lipoprotein metabolism (dyslipidemia) can result in premature atherosclerosis or pancreatitis. Dyslipidemias can be classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low density lipoprotein cholesterol and decreased levels of HDL cholesterol predispose to premature atherosclerosis. Triglyceride levels greater than 1,000 mg/dL increase the risk for pancreatitis. In the appraisal of the dyslipidemias, measurement of serum cholesterol, triglycerides, HDL-cholesterol and obtaining the LDL cholesterol by Friedewald equation is usually sufficient in the majority of patients. However, in some cases, such as the diagnosis of the Type III dyslipidemia and when triglycerides are > or = 400 mg/dL, ultracentrifugation is required to determine the VLDL or LDL cholesterol. Lipoprotein electrophoresis can be useful in the diagnosis of Type III dyslipidemia (broad beta band) and also to detect chylomicrons. In young subjects with coronary artery disease with a normal LDL cholesterol an apolipoprotein B-100 level may be a useful test. In children and young adults with severe hypertriglyceridemia, measurement of lipoprotein lipase activity or assaying apolipoprotein C-II levels can be useful in elucidating the cause. Also, laboratory tests are useful in excluding a secondary cause of dyslipidemia (urinalysis, plasma creatinine, TSH, glucose, protein electrophoresis, alkaline phosphatase and transaminases). Thus, laboratory investigations play an important role in the management of dyslipidemia.
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PMID:A practical approach to the laboratory diagnosis of dyslipidemia. 870 23

The effect of the apolipoprotein C-II/C-III1 ratio on the capacity of purified bovine milk lipoprotein lipase to hydrolyse triglycerides was measured in a controlled model of pyrene-labeled nonanoyltriglycerides (1-2 ditetradecyl 3-pyrene nonanoyl glyceride) monolayer vesicles. Monolayer was composed of triglycerides, a non-hydrolysable phospholipid ether and cholesterol, a model system where the quality of the interface can be controlled. LPL released fatty acids from pyrene-triglycerides which were transferred from the lipoprotein structure to albumin. This transfer induces a decrease in the excimer production and in the excimer fluorescence intensity. Apolipoprotein C-II and C-III0 and C-III1 were purified from apolipoprotein VLDL. The 2 fragments, C-III1 A (peptide 1-40) and C-III1 B (peptide 41-79), were obtained after thrombin cleavage. Apolipoproteins C-III0 and C-III1 had a similar inhibitory effect on LPL. Inhibition with apo C-III0 or apo C-III1 was 85% of full LPL activity without inhibitor: Apo C-III1 B inhibited 62% of basal activity. It was 27% less effective than apo C-III1. Fragment C-III1 A did not inhibit LPL. The effect of change in both apo C-II (0-0.6 microM) and apo C-III1 (0-1.0 microM) on triglyceride hydrolysis shows the importance of the apo C-II/C-III1 ratio for the release of free fatty acids from triglycerides by LPL. The activating effect of apo C-II in the absence of the apo C-III inhibitor was maximal at 0.06 microM. No further activation was obtained between 0.06 and 0.30 microM. Higher concentrations decreased LPL activity. Apo C-III1 (0.1 microM) decreased the maximum activation by apo C-II from 0.0196 to 0.063 nmol/min/nmol LPL. Higher concentrations of apo C-III1 (0.1-0.5 microM) required higher apo C-II concentrations (0.30 microM instead of 0.06 microM) for maximal activation than when apo C-III1 was absent. The activity of the enzyme without apo C-II was decreased by 65% by 0.12 microM apo C-III1. Increasing the apo C-II/apo C-III1 ratio from 0.1 to 1, increased the activation of the enzyme by a given apo C-II concentration. Moreover, for a given apo C-II/C-III1 ratio, the LPL activation increased with the apo C-II concentration (between 0 and 0.010 microM), until a plateau was reached. This is important, as the change in the C-II/C-III1 ratio is not the only factor affecting LPL activity, and inhibition by apo C-III1 also depends on the overall quantity of apolipoproteins. Extrapolation of these results suggests that hyperlipoproteinemia seems to be more likely due to overproduction of VLDL, than to a decrease in lipoprotein lipase activity.
Atherosclerosis 1996 Dec 20
PMID:Effect of the apolipoprotein C-II/C-III1 ratio on the capacity of purified milk lipoprotein lipase to hydrolyse triglycerides in monolayer vesicles. 912 10


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