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

Marian C. Cheung, Armando J Mendez, Anitra C. Wolf, Robert H. Knopp

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33 Citations (Scopus)

Abstract

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 AII); one contained apo A-I but no A-II, Lp(AI w/o AII); and the third (an unusual one) contained apo A-II 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 AII) and Lp(AIw / oAII) were present in the plasma of the relatives. AII 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 nonHDL plasma fractions. These findings are discussed in light of Tangier disease and other known HDL-deficiency cases, and the role of HDL in the maintenance of cell cholesterol homeostasis.

Original languageEnglish
Pages (from-to)522-529
Number of pages8
JournalJournal of Clinical Investigation
Volume91
Issue number2
StatePublished - Feb 1 1993
Externally publishedYes

Fingerprint

Tangier Disease
Apolipoprotein A-I
Cholesterol
HDL Cholesterol
Triglycerides
Apolipoproteins D
Apolipoprotein A-II
Phosphatidylcholine-Sterol O-Acyltransferase
Corneal Opacity
Lipids
Immunosorbents
Aptitude
Hepatomegaly
Esterification
Palatine Tonsil
Splenomegaly
Peripheral Nervous System Diseases
lipoprotein A-II
Familial HDL deficiency
Population

Keywords

  • Cell cholesterol esterification
  • Coronary artery disease
  • High density lipoprotein subpopulations
  • Immunoaffinity chromatography
  • Lecithin cholesterol acyltransferase

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{e7ed1ceb244146849a9b59f035b04d5b,
title = "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",
abstract = "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 AII); one contained apo A-I but no A-II, Lp(AI w/o AII); and the third (an unusual one) contained apo A-II 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 AII) and Lp(AIw / oAII) were present in the plasma of the relatives. AII 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 nonHDL plasma fractions. These findings are discussed in light of Tangier disease and other known HDL-deficiency cases, and the role of HDL in the maintenance of cell cholesterol homeostasis.",
keywords = "Cell cholesterol esterification, Coronary artery disease, High density lipoprotein subpopulations, Immunoaffinity chromatography, Lecithin cholesterol acyltransferase",
author = "Cheung, {Marian C.} and Mendez, {Armando J} and Wolf, {Anitra C.} and Knopp, {Robert H.}",
year = "1993",
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language = "English",
volume = "91",
pages = "522--529",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
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TY - JOUR

T1 - 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

AU - Cheung, Marian C.

AU - Mendez, Armando J

AU - Wolf, Anitra C.

AU - Knopp, Robert H.

PY - 1993/2/1

Y1 - 1993/2/1

N2 - 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 AII); one contained apo A-I but no A-II, Lp(AI w/o AII); and the third (an unusual one) contained apo A-II 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 AII) and Lp(AIw / oAII) were present in the plasma of the relatives. AII 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 nonHDL plasma fractions. These findings are discussed in light of Tangier disease and other known HDL-deficiency cases, and the role of HDL in the maintenance of cell cholesterol homeostasis.

AB - 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 AII); one contained apo A-I but no A-II, Lp(AI w/o AII); and the third (an unusual one) contained apo A-II 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 AII) and Lp(AIw / oAII) were present in the plasma of the relatives. AII 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 nonHDL plasma fractions. These findings are discussed in light of Tangier disease and other known HDL-deficiency cases, and the role of HDL in the maintenance of cell cholesterol homeostasis.

KW - Cell cholesterol esterification

KW - Coronary artery disease

KW - High density lipoprotein subpopulations

KW - Immunoaffinity chromatography

KW - Lecithin cholesterol acyltransferase

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