Isolation and Characterization of an Abnormal High Density Lipoprotein in Tangier Disease

Assmann, Gerd; Herbert, Peter N.; Fredrickson, Donald S.; Forte, Trudy M.

doi:10.1172/jci108761

Cited by 83 publications

(43 citation statements)

References 43 publications

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“…These lipoproteins would be predicted to float at density 1.21 g/ml in the ultracentrifuge. Thus, the nature of the A-I-and/ or A-Il-containing particles in IM appeared to be comparable to those in a subject with apo A-I deficiency heterozygous for a 45-bp deletion in exon 4 of the apo A-I gene (38) and in Tangier disease where most ofthe A-Il was reported to be located in the plasma lipoproteins with alpha electrophoretic mobility whereas most of the A-I was found in the lipoprotein-free plasma fraction and migrated with prebeta mobility (46,47 The distribution of all four usually "HDL-associated" proteins was somewhat abnormal in the patient. First, most of her A-I and A-Il were found in separate particles whereas, in normal individuals, approximately two thirds of A-I and essentially all A-II were associated with each other (7,9,32).…”

Section: Resultsmentioning

confidence: 60%

Characterization of apolipoprotein A-I- and A-II-containing lipoproteins in a new case of high density lipoprotein deficiency resembling Tangier disease and their effects on intracellular cholesterol efflux.

et al. 1993

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A 48-yr-old Caucasian female of central European origin (subject IM) with low plasma cholesterol and normal plasma triglyceride (TG) had extremely low apo A-I (6 mg/dl), A-II (5 mg/dl), and HDL cholesterol (2 mg/dl) levels. She had most of the clinical symptoms typically associated with Tangier disease, including early corneal opacities, yellow-streaked tonsils, hepatomegaly, and variable degrees of peripheral neuropathy, but had no splenomegaly. She had a myocardial infarction at age 46. Since HDL are postulated to be involved in the transport of excess cholesterol from peripheral tissues to the liver for degradation, and the ability of an HDL particle to promote cellular cholesterol efflux appears to be related to its density, size, and apo A-I and A-II contents, we isolated and characterized the HDL particles of this patient and all her first degree relatives (mother, a brother, and two children). The plasma A-I, A-II, and HDL cholesterol levels of all five relatives were either normal or high. Using anti-A-I and anti-A-II immunosorbents, we found three populations of particles in IM: one contained both apo A-I and A-II, Lp(AI w All); one contained apo A-I but no A-II, Lp(AI w/o All); and the third (an unusual one) contained apo A-Il but no A-I, Lp(AII). Two-thirds of her plasma A-I and A-II existed in separate HDL particles, i.e., in Lp(AI w/o AII) and Lp(AII), respectively. Only Lp(AI w All) and Lp(AI w/o All) were present in the plasma of the relatives. All three populations of the patient's HDL particles had a normal core/ surface lipid ratio, but the cores were enriched with TG. The apo A-I-containing particles, however, were considerably smaller and contained much less lipid than Lp(AII). Despite these unusual physicochemical characteristics, the apo A-I-containing particles and Lp(AII) were effective suppressors of intracellular cholesterol esterification in cholesterol-loaded human skin fibroblast. The patient's plasma apo D and lecithin cholesterol acyltransferase levels were reduced, with an increased proportion located in non-HDL plasma fractions. These findings are discussed in light of

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Section: Resultsmentioning

confidence: 60%

Characterization of apolipoprotein A-I- and A-II-containing lipoproteins in a new case of high density lipoprotein deficiency resembling Tangier disease and their effects on intracellular cholesterol efflux.

et al. 1993

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“…However, it is unknown whether apoC phospholipids and unesterified cholesterol are removed from VLDL in a particulated form, or whether the disks represent lipid:protein associations formed after the removal of unassociated molecules as seen in vitro (46,47). Yet it is interesting to note that disk-shaped lipoproteins were found in plasma of patients with either familial HDL deficiency (48,49) or familial lecithin: cholesterol acyltransferase deficiency (43)(44)(45), and that in these conditions the amount of disks seems to vary in proportion to the amount of fat in the diet (45,49 …”

Section: Discussionmentioning

confidence: 99%

Very Low Density Lipoprotein

Chajek¹,

Eisenberg²

1978

J. Clin. Invest.

143

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“…135 Subsequently, an HDL particle containing apo A-ll, but no apo A-l, was noted in Tangier homozygotes after HDL isolation by ultracentrifugation. 136 In addition, it was reported 129 ' 130 that a large fraction of apo A-l in Tangier plasma was found in the 1.21 g/ml infranate. Other studies confirmed this finding, but also reported 131 that 28% of apo A-l and 9 1 % of apo A-ll in the plasma of homozygotes was found in the 1.063 g/ml supemate.…”

Section: Tangier Diseasementioning

confidence: 99%

Clinical, biochemical, and genetic features in familial disorders of high density lipoprotein deficiency.

Schaefer¹

1984

Arteriosclerosis

162

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P lasma high density lipoproteins (HDL, density = 1.063 -1.21 g/ml) mostly have alpha mobility on lipoprotein electrophoresis, and are composed (weight %) of approximately 50% protein, 25% phospholipid, 20% cholesterol (mainly esterified), and triglyceride. 1 " 1 Fluctuations in HDL levels have been associated largely with alterations in HDL (d = 1.063-1.125 g/ml). 5 Cholesterol is the HDL constituent commonly measured (following precipitation of other lipoproteins), and decreased plasma HDL cholesterol concentrations have been associated with premature coronary artery disease (CAD).*" 11 The normal values for this parameter are given in Table 1.

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Isolation and Characterization of an Abnormal High Density Lipoprotein in Tangier Disease

Cited by 83 publications

References 43 publications

Characterization of apolipoprotein A-I- and A-II-containing lipoproteins in a new case of high density lipoprotein deficiency resembling Tangier disease and their effects on intracellular cholesterol efflux.

Characterization of apolipoprotein A-I- and A-II-containing lipoproteins in a new case of high density lipoprotein deficiency resembling Tangier disease and their effects on intracellular cholesterol efflux.

Very Low Density Lipoprotein

Clinical, biochemical, and genetic features in familial disorders of high density lipoprotein deficiency.

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