Characterization of high density lipoproteins in patients heterozygous for Tangier disease.

Assmann, Gerd; Simantke, O; Schaefer, Heinz-Guenther; Smootz, E

doi:10.1172/jci108853

Cited by 54 publications

(23 citation statements)

References 24 publications

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“…Studies on obligate TD heterozygotes have reported conflicting findings (19,22). In our large cohort, symptomatic vascular disease was over three times as frequent in the adult heterozygotes as in unaffected family members (Table 1).…”

Section: Abca1 Heterozygotes Have Decreased Hdl Cholesterol and An Inmentioning

confidence: 67%

“…As many factors, both genetic and environmental, influence plasma HDL-C levels and contribute to low HDL-C values, unambiguous identification of heterozygotes for ABCA1 mutations has until now been impossible. Individuals from TD kindreds presumed to be heterozygous have shown a range of phenotypes, and much overlap with unaffected individuals has been seen (19)(20)(21), possibly reflecting the fact that some individuals had been misclassified. Indeed, the inability to uniquely identify heterozygous individuals created difficulty in mapping the gene for TD (15).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, the inability to uniquely identify heterozygous individuals created difficulty in mapping the gene for TD (15). Studies in obligate heterozygotes have also been limited to small numbers (22), often within a single family (19), and thus restricted in the ability to analyze the phenotypic expression with different mutations and over a range of ages.…”

Section: Introductionmentioning

confidence: 99%

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Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes

Clee¹,

Kastelein²,

Dam³

et al. 2000

J. Clin. Invest.

300

188

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Section: Abca1 Heterozygotes Have Decreased Hdl Cholesterol and An Inmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes

Clee¹,

Kastelein²,

Dam³

et al. 2000

J. Clin. Invest.

300

188

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“…Some insights into the molecular events controlling this turnover process came from studies in patients with Tangier disease, a genetic illness characterized by a marked reduction in the level of circulating apolipoprotein AI (apoAI) and cholesterol carried in HDL (HDL-C) and by tissue infiltration of lipid-laden macrophages (14). With the discovery that this disease was apparently caused by mutations in the transport protein ABCA1 (15)(16)(17)(18), a fairly straightforward paradigm was developed to describe the putative events characterizing so-called "reverse cholesterol transport."…”

mentioning

confidence: 99%

ABCA1 plays no role in the centripetal movement of cholesterol from peripheral tissues to the liver and intestine in the mouse

Xie

Turley

Dietschy

2009

Journal of Lipid Research

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This study uses the mouse to explore the role of ABCA1 in the movement of this cholesterol from the peripheral organs to the endocrine glands for hormone synthesis and liver for excretion. The sterol pool in all peripheral organs was constant and equaled 2,218 and 2,269 mg/kg, respectively, in abca1 1/1 and abca1 2/2 mice. Flux of cholesterol from these tissues equaled the rate of synthesis plus the rate of LDL-cholesterol uptake and was 49.9 mg/day/kg in control animals and 62.0 mg/day/kg in abca1 2/2 mice. In the abca1 1/1 animals, this amount of cholesterol moved from HDL into the liver for excretion. In the abca1 2/2 mice, the cholesterol from the periphery also reached the liver but did not use HDL. Fecal excretion of cholesterol was just as high in abac1 2/2 mice (198 mg/day/kg) as in the abac1animals (163 mg/day/kg), although the abac1 2/2 mice excreted relatively more neutral than acidic sterols. This study established that ABCA1 plays essentially no role in the turnover of cholesterol in peripheral organs or in the centripetal movement of this sterol to the endocrine glands, liver, and intestinal tract for excretion.-Xie, C., S. D. Turley, and J. M. Dietschy. ABCA1 plays no role in the centripetal movement of cholesterol from peripheral tissues to the liver and intestine in the mouse. J. Lipid Res. 2009Res. . 50: 1316Res. -1329

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“…Major serum abnormalities noted in homozygous abnormal patients include hypocholesterolemia, hypertriglyceridemia, the absence of a-migrating-lipoproteins on agarose electrophoresis, and decreased apolipoprotein A-I (apoA-I) concentrations (1,3,4,6,7). In obligate Tangier heterozygotes, HDL cholesterol and apoA-I concentrations are reduced to 50% of controls (2,8).…”

mentioning

confidence: 99%

Tangier disease: a disorder of intracellular membrane traffic.

Schmitz¹,

Assmann²,

Robenek³

et al. 1985

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

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100

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The interaction of human high density lipoproteins (HDL) with isolated human monocytes from control and Tangier patients was studied in tissue culture experiments. It was observed that normal monocytes, similar to mouse peritoneal macrophages, bind HDL to a cell surface receptor, internalize the bound HDL particles, transport the internalized HDL intracellularly through the cytoplasmic compartment without significant degradation, and ultimately resecrete intact HDL. The cellular interaction of Tangier monocytes with normal HDL was markedly different from control monocytes. HDL binding to Tangier monocytes was moderately increased and cell-associated HDL radioactivity was 6-to 10-fold enhanced in Tangier monocytes. The bulk of the internalized HDL, however, was detected in secondary lysosomes. Only minor amounts of the internalized HDL were resecreted from the Tangier monocytes, and most of this was degraded. These data suggest that the cellular metabolism of HDL is abnormal in Tangier monocytes. It is postulated that Tangier disease may be a disorder of intracellular membrane traffic in which HDL is diverted into the lysosomal compartment and degraded instead of being secreted through its regular transcellular route.Tangier disease is a rare, autosomal recessive disorder of serum lipoprotein metabolism characterized by the complete absence of normal high density lipoproteins (HDL) from serum and a great increase in the cellular concentration of cholesteryl esters in macrophages and Schwann cells of peripheral nerves (1-5). Patients have large pharyngeal tonsils, splenomegaly, and transient peripheral neuropathy (1-4). Major serum abnormalities noted in homozygous abnormal patients include hypocholesterolemia, hypertriglyceridemia, the absence of a-migrating-lipoproteins on agarose electrophoresis, and decreased apolipoprotein A-I (apoA-I) concentrations (1, 3, 4, 6, 7). In obligate Tangier heterozygotes, HDL cholesterol and apoA-I concentrations are reduced to 50% of controls (2, 8).Several hypotheses have been formulated to explain the molecular defect in Tangier disease. These include (i) accelerated catabolism of HDL despite normal rates of apoA-I synthesis (6, 9-12), (ii) abnormal structure ofapoA-I (13), (iii) impaired interconversion of proapoA-I to mature apoA-I (14-17), and (iv) a failure ofproapoA-I to associate with HDL (18,19 Recent experiments suggest that HDL bind to specific cellular receptors on fibroblasts, arterial smooth muscle cells (20,21), and macrophages (22). Our preliminary studies with macrophages revealed that, subsequent to receptor-mediated binding, HDL are internalized and resecreted after prior interaction with cytoplasmic cholesteryl ester droplets. This is in contrast to low density lipoproteins (LDL), which are degraded in the lysosomal compartment after uptake. The detailed molecular events ofthe retroendocytosis of HDL are not yet understood. We here report upon studies of the interaction of serum HDL with human blood monocytes, the precursor cells of tissue macrophages...

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Characterization of high density lipoproteins in patients heterozygous for Tangier disease.

Cited by 54 publications

References 24 publications

Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes

Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes

ABCA1 plays no role in the centripetal movement of cholesterol from peripheral tissues to the liver and intestine in the mouse

Tangier disease: a disorder of intracellular membrane traffic.

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