Effects of estrogen therapy on apolipoprotein E in type III hyperlipoproteinemia

Falko, James M.; Schonfeld, Gustav; Witztum, Joseph L.; Kolár, J; Weidman, Stuart W.

doi:10.1016/0026-0495(79)90158-6

Cited by 34 publications

(15 citation statements)

References 25 publications

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“…Recently KASHYAP Our observations disagree with the report of FALKO et al [9] who failed to observe any changes in the apo CII/apo CIII mass ratio in the serum and lipoproteins d < 1.006 in response to high-carbohydrate diet (85 % of energy supply) in normolipaemic subjects and in patients with hyperlipoproteinaemia type 111 and type IV. The divergence of the results could depend on the difference in the nutrition pattern between both studies, and also on the conditions of blood sampling.…”

Section: Discussioncontrasting

confidence: 93%

The effect of short‐term and prolonged fructose intake on VLDL‐TG and relative properties on apo CIII₁ and apo CII in the VLDL fraction in type IV hyperlipoproteinaemia

Cybulska

Naruszewicz

1982

Nahrung

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Twenty two patients with hyperlipoproteinaemia type IV consumed fructose in a daily dose of 80 g for 28 days. Apart from that they kept their normal diet. We observed the considerable heterogeneity of hyperlipaemic responses of patients under study after 7 days of fructose feeding. However VLDL-TG and the relative ratio apo CIII1/apo CII in VLDL increased in the whole group. The rise in serum VLDL was associated with a fall in LDL-Chol and HDL-Chol. After extention of fructose intake to 28 days a decrease of VLDL-TG with concomitant fall of the relative ratio apo CIII1/apo CII in VLDL was found. LDL-Chol increased. Our observations point to the reversibility of fructose-induced changes in the lipoprotein composition after prolongation of its intake.

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Section: Discussioncontrasting

confidence: 93%

The effect of short‐term and prolonged fructose intake on VLDL‐TG and relative properties on apo CIII₁ and apo CII in the VLDL fraction in type IV hyperlipoproteinaemia

Cybulska

Naruszewicz

1982

Nahrung

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“…Treatment of women with familial dysf3LP with physiological amounts of estrogen reduces the concentration of remnant-like lipoproteins, sometimes dramatically (27,28). Estrogen treatment of our rats produced a small and variable stimulation of the hepatic uptake of apo E from patients with dys3LP.…”

Section: Discussionmentioning

confidence: 75%

Isoprotein specificity in the hepatic uptake of apolipoprotein E and the pathogenesis of familial dysbetalipoproteinemia.

Havel¹,

Chao²,

Windler³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

162

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The uptake and catabolism of lamellar complexes of rat 12MI4abeled apolipoprotein (apo) E with egg lecithin were increased severalfold in perfused livers of rats given large amounts of 17a-ethynylestradiol for 5 days. Estrogen-stimulated uptake of lamellar complexes of human apo E that contained al of the major normally occurring "isoforms" of the protein (apo E-1, E-2, E-3, and E4) was comparable to that of rat apo E. By contrast, uptake of complexes containing apo E from individuals with familial dysbetalipoproteinemia (dys#LP; characterized by a lack of apo E-3 and E4) was stimulated to a much smaller extent. With complexes containing individual isoforms of human apo E, it was shown that estrogen-stimulated hepatic uptake was largely confined to apo E-3 and E4; uptake of apo The metabolism of triglyceride-rich lipoproteins in the blood plasma of rats proceeds in two distinct steps (1). In the first, triglycerides in the core of the particles are removed in extrahepatic tissues by the action of lipoprotein lipase. In the second, the modified "remnant" lipoproteins are rapidly taken up by the liver or, at least in the case of hepatogenous very low density lipoproteins (VLDL), are converted in part to low density lipoproteins (LDL). During the first step, most of the apolipoproteins of small molecular weight (C apoproteins) are removed and transferred to high density lipoproteins (HDL). When the VLDL are converted to LDL, the arginine-rich apolipoprotein (apo E) is removed and the high molecular weight apolipoprotein (apo B) remains as the only protein component. Remnant lipoproteins containing apo E and apo B are rapidly taken up by the liver, whereas LDL that contain only apo B are removed very slowly from the blood, and it has been suggested that apo E is an important determinant of the hepatic uptake of remnant lipoproteins (2, 3). Uptake of chylomicron remnants by the perfused rat liver is saturable, consistent with a receptor-dependent process (4, 5). Indirect evidence suggests that the metabolism of triglyceride-rich lipoproteins in humans proceeds in the same two steps (1, 2, 6).In familial dysbetalipoproteinemia (dysfLP), a monogenic human disorder of lipoprotein metabolism, particles with the properties of remnants of chylomicrons and VLDL accumulate in the blood, and the concentration of LDL is reduced (2). Thus, when compared with their putative precursors, these particles are characterized by a higher ratio of cholesteryl esters to triglycerides in their core (7) and by an increased proportion of apo E on their surface (8). As shown by isoelectric focusing techniques (9, 10), apo E is normally composed of three or four major "isoforms" (apo E-1, E-2, E-3, and E-4). Apo E-4 is present in only about 25% of normal persons (variant trait). In familial dys(LP, apo E is grossly deficient or lacking in both apo E-3 and E-4, which raises the possibility that a structural abnormality of this protein impairs the hepatic uptake of remnants and their conversion to LDL.Recent research has shown that trea...

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“…For example, type III hyperlipoproteinemia in women most often occurs after menopause (21), and in these individuals the disorder is particularly responsive to estrogen therapy (34)(35)(36). The induction of hepatic apo-B,E receptors in animals given estrogen, though at nonpharmacologic doses, has previously been reported (37,38).…”

Section: Discussionmentioning

confidence: 96%

Identical Structural and Receptor Binding Defects in Apolipoprotein E2 in Hypo-, Normo-, and Hypercholesterolemic Dysbetalipoproteinemia

Rall¹,

Weisgraber²,

Innerarity³

et al. 1983

J. Clin. Invest.

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A B S T R A c T Apolipoprotein E (apoprotein E or apo-E) from type III hyperlipoproteinemic subjects with the E2/2 homnozygous phenotype displays both structural and receptor binding heterogeneity. The apo-E from all subjects thus far studied, however, has been functionally defective, though to different degrees. Although nearly every type 111 hyperlipoproteinemic subject has the E2/2 phenotype, 95-99% of the people with this same phenotype do not display type 111 hyperlipoproteinemia, nor do they have elevated plasma cholesterol levels. Consequently, it became important to determine whether the apo-E2 from hypo-and normocholesterolemic individuals with the E2/2 phenotype is also functionally abnormal. To do this, apo-E2 was isolated from two hypo-, two normo-, and two hy percholesterolemic homozygous E2/2 subjects. The apo-E2 was recombined with phospholipid vesicles and tested for its ability to displace l251 -Iio density lipoproteins (LDL) from apo-B,E (LDL) receptors on human fibroblasts. The apo-E2 from all six subjects was found to be severely defective in receptor binding (<2% of the binding activity of normal apo-E-3). In all cases, the binding activity of the apo-E2 was increased 10-to 20-fold by treating the apoproteins with cysteamine, a reagent that converts cysteine residues to positively charged lysine analogues. The cxsteine content of each apo-E wsas determined by monitoring the .Xddress corresp)ondenec to Dr. Mlahlev. R ccciLed for publicat ion 22 Oct obe r 1982. change in the isoelectric focusing position of the cysteamine-treated apo-E2. Using this method, it was found that the apo-E2 from each subject contained two cysteine residues per mole. A partial sequence analysis of the cysteine-containing regions of the apo-E from three of the six subjects indicated that the two cysteine residues were at residues 112 and 158 in the amino acid sequence. The cysteine at residue 158 has previously been implicated in the severe binding defect of the apo-E2 from a type III hyperlipoproteinemic subject. Since the apo-E2 of the hvpo-, normo-, and hypercholesterolemic subjects in this study all displayed a severe functional abnormality, it is apparent that factors in addition to the defective receptor binding activity of the apo-E2 are necessary for the manifestation of type III hyperlipoproteinenmia. I N TRODUCT IONThe complex isoform pattern displayed by human apolipoprotein E (apoprotein E or apo-E)' is due to primary structural differences and posttranslational modification. Utermann and his colleagues (1-3) were the first to demonstrate the genetic polymorphism of the apo-E isoforms. Since then, evidence has been presented to show that this genetic polymorphism results from the presence of multiple alleles at a single genetic Abbreviationl.s used in this paper: apo, apolipoprotein; I)\1I(, (liluvN\risto\ llhosl)haitidvicholine.J. Clin. Invest.

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Effects of estrogen therapy on apolipoprotein E in type III hyperlipoproteinemia

Cited by 34 publications

References 25 publications

The effect of short‐term and prolonged fructose intake on VLDL‐TG and relative properties on apo CIII₁ and apo CII in the VLDL fraction in type IV hyperlipoproteinaemia

The effect of short‐term and prolonged fructose intake on VLDL‐TG and relative properties on apo CIII₁ and apo CII in the VLDL fraction in type IV hyperlipoproteinaemia

Isoprotein specificity in the hepatic uptake of apolipoprotein E and the pathogenesis of familial dysbetalipoproteinemia.

Identical Structural and Receptor Binding Defects in Apolipoprotein E2 in Hypo-, Normo-, and Hypercholesterolemic Dysbetalipoproteinemia

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Effects of estrogen therapy on apolipoprotein E in type III hyperlipoproteinemia

Cited by 34 publications

References 25 publications

The effect of short‐term and prolonged fructose intake on VLDL‐TG and relative properties on apo CIII1 and apo CII in the VLDL fraction in type IV hyperlipoproteinaemia

The effect of short‐term and prolonged fructose intake on VLDL‐TG and relative properties on apo CIII1 and apo CII in the VLDL fraction in type IV hyperlipoproteinaemia

Isoprotein specificity in the hepatic uptake of apolipoprotein E and the pathogenesis of familial dysbetalipoproteinemia.

Identical Structural and Receptor Binding Defects in Apolipoprotein E2 in Hypo-, Normo-, and Hypercholesterolemic Dysbetalipoproteinemia

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The effect of short‐term and prolonged fructose intake on VLDL‐TG and relative properties on apo CIII₁ and apo CII in the VLDL fraction in type IV hyperlipoproteinaemia

The effect of short‐term and prolonged fructose intake on VLDL‐TG and relative properties on apo CIII₁ and apo CII in the VLDL fraction in type IV hyperlipoproteinaemia