Characterization of low-density-lipoprotein in apolipoprotein E deficiency in a patient without coronary atherosclerosis

Teramoto, Tamio; Kinoshita, Makoto; Kawamura, Mitsunobu; Liang, Yi-Qiang; Kaneko, Kazuko; Shimazu, Nobuko; Suga, Satoko; Akatuka, N; Yamanaka, Masami

doi:10.1016/0009-8981(95)06239-4

Cited by 2 publications

(6 citation statements)

References 15 publications

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“…However, in a patient with apo E deficiency as well as the patients with type III hyperlipidemia, atherosclerosis and xanthomas are observed despite low LDL-cholesterol levels in the plasma. The LDL from an apo E-deficient patient showed no difference in susceptibility to oxidative modification compared to that from normal controls (2). In the present study, we analyzed the mechanism of xanthoma formation and the progression of atherosclerosis that was observed in an apo E-deficient patient despite low levels Table 3.…”

Section: Discussionmentioning

confidence: 99%

“…A patient with congenitally deficient aplipoprotein (apo) E showed type III hyperlipidemia with a marked increase of very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL), which both contained more cholesterol than those from normal controls (1,2). Although the LDL-cholesterol level was low, the patient showed numerous xanthomas as well as atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

“…It has already been reported that an apo E-deficient patient had low plasma LDL-cholesterol levels and that there was no difference in the susceptibility to oxidative modification between LDLs from the apo E deficient patient and normal controls (1,2). To elucidate the mechanism of xanthoma formation observed in the apo E deficient patient, we studied the foam cell formation ability of accumulated VLDL from an apo E deficient patient and as well as the cholesterol efflux ability of HDL in that patient.…”

Section: Introductionmentioning

confidence: 99%

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Apotipoprotein E Accelerates the Efflux of Cholesterol from Macrophages : Mechanism of Xanthoma Formation in Apolipoprotein E Deficiency

Kinoshita

Kawamura

Maeda

et al. 2000

J Atheroscler Thromb

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A patient with congenitally deficient apolipoprotein (apo) E showed numerous tuberoerutive, tendon xanthomas and severe atherosclerosis, despite a low LDL concentration.In order to study the mechanism of xanthoma formation observed in apo E-deficient patients, we evaluated the effect of VLDL and HDL from the patient on cholesterol ester (CE) accumulation in macrophages.The results showed that there was no difference in CE formation in macrophages among normal VLDL, the patient's VLDL and apo E containing VLDL, which was prepared by incubation of the patient's VLDL with recombinant apo E. On the other hand, apo E containing HDL, which was prepared by incubation of the patient's HDL with recombinant apo E, accelerated cholesterol efflux more effectively than did the patient's HDL and decreased intracellular CE content. Moreover, free apo E accelerated cholesterol efflux from lipid loaded macrophages.These results suggest that macrophages are prevented from transforming into foam cells by their secretion of apo E. This may also explain the marked atherosclerosis and xanthomatosis observed in the patient with apo Edeficiency.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Apotipoprotein E Accelerates the Efflux of Cholesterol from Macrophages : Mechanism of Xanthoma Formation in Apolipoprotein E Deficiency

Kinoshita

Kawamura

Maeda

et al. 2000

J Atheroscler Thromb

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“…Supporting this surprising finding is a study by Tomiyasu et al (35), which showed an increased direct removal of large VLDL without apoE as compared with those with apoE. By electron microscopy, VLDL in apoE-deficient subjects are more heterogeneous in size as compared with "classic" type III hyperlipidemia or healthy controls (10,31,36). Inhibition of direct removal of IDL apoB-100 is supported by a kinetic study by Turner et al (37) using dyslipidemic E2 homozygotes, but not by the other study by Demant et al (38) using normolipidemic E2 homozygotes.…”

Section: Lp(a) Metabolismmentioning

confidence: 95%

“…In studies with the apoE-deficient subject and control subject #7, blood sampling continued at 18,24,36,48, 72, 96, 120, and 168 h. During the infusion, meals were served in equal small portions every 2 h. Plasma was immediately separated by centrifugation at 2,300 rpm for 30 min at 4 Њ C. VLDL, IDL, and LDL were isolated by sequential ultracentrifugation from 5 ml of plasma and processed for the analysis by gas chromatographymass spectrometry (GC-MS) as previously described (19,20). Briefly, lipoproteins were dialyzed against 10 mM ammonium bicarbonate, lyophilized, and delipidated.…”

Section: Apob-100 and Apob-48 Kinetic Study Using Stable Isotopicallymentioning

confidence: 99%

Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiency

Ikewaki

Cain

Fairwell

et al. 2004

Journal of Lipid Research

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The present study was undertaken to elucidate the metabolic basis for the increased remnants and lipoprotein(a) [Lp(a)] and decreased LDL apolipoprotein B (apoB) levels in human apoE deficiency. A primed constant infusion of 13 C 6 -phenylalanine was administered to a homozygous apoE-deficient subject. apoB-100 and apoB-48 were isolated, and tracer enrichments were determined by gas chromatography-mass spectrometry, then kinetic parameters were calculated by multicompartmental modeling. In the apoE-deficient subject, fractional catabolic rates (FCRs) of apoB-100 in VLDL and intermediate density lipoprotein and apoB-48 in VLDL were 3 ؋ , 12 ؋ , and 12 ؋ slower than those of controls. On the other hand, the LDL apoB-100 FCR was increased by 2.6 ؋ . The production rate of VLDL apoB-100 was decreased by 45%. In the Lp(a) kinetic study, two types of Lp(a) were isolated from plasma with apoE deficiency: buoyant and normal Lp(a). 125 I-buoyant Lp(a) was catabolized at a slower rate in the patient. However, 125 Ibuoyant Lp(a) was catabolized at twice as fast as 131 I-normal Lp(a) in the control subjects.In summary, apoE deficiency results in: 1) a markedly impaired catabolism of VLDL/chylomicron and their remnants due to lack of direct removal and impaired lipolysis; 2) an increased rate of catabolism of LDL apoB-100, likely due to upregulation of LDL receptor activity; 3) reduced VLDL apoB production; and 4) a delayed catabolism of a portion of Lp(a). Apolipoprotein E (apoE) functions as the ligand for receptors, including LDL receptor-related protein (LRP), VLDL receptor, and LDL receptor (1, 2), and is thus important for the metabolism of apoB-containing lipoproteins. apoE is also considered to be important for the lipolysis of triglyceride (TG)-rich lipoproteins (3-6) and has been reported to facilitate VLDL production in animal models (7,8). apoE knockout mice have elevated VLDL and remnants and developed atherosclerosis on a chow diet (9). There have been several reported cases of humans with genetic apoE deficiency (10). All cases have type III hyperlipoproteinemia and some of the patients developed premature atherosclerosis in favor of the concept that apoE is crucial in human lipoprotein metabolism.Two kinetic studies in apoE-deficient subjects have been reported. Schaefer et al. (10) performed a radiotracer study and reported an impaired VLDL metabolism, in particular apoB-48, in a single apoE-deficient patient. However, multicompartmental modeling was not employed, thus only VLDL apoB-100 and apo-B48 were mathematically analyzed. Gabelli et al. (11) reported, in an LDL kinetic study using the same patient, that the rate of catabolism of LDL apoB was increased in the apoE-deficiency patient despite the relatively lower affinity of the LDL particles for the LDL receptor. However, an overall scheme of apoB-containing lipoprotein metabolism in humans with apoE deficiency has not been established. To establish the effect of apoE deficiency on apoB-containing lipoproteins, we performed an in vivo kinetic ...

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Characterization of low-density-lipoprotein in apolipoprotein E deficiency in a patient without coronary atherosclerosis

Cited by 2 publications

References 15 publications

Apotipoprotein E Accelerates the Efflux of Cholesterol from Macrophages : Mechanism of Xanthoma Formation in Apolipoprotein E Deficiency

Apotipoprotein E Accelerates the Efflux of Cholesterol from Macrophages : Mechanism of Xanthoma Formation in Apolipoprotein E Deficiency

Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiency

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