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| Content Provider | PubMed Central |
|---|---|
| Author | Cheung, M. C. Mendez, A. J. Wolf, A. C. Knopp, R. H. |
| 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(AI w/o AII) 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 Tangier disease and other known HDL-deficiency cases, and the role of HDL in the maintenance of cell cholesterol homeostasis. |
| Related Links | http://dx.doi.org/10.1172/jci116231 |
| Ending Page | 529 |
| Page Count | 8 |
| Starting Page | 522 |
| File Format | |
| ISSN | 00219738 |
| Journal | Journal of Clinical Investigation |
| Issue Number | 2 |
| Volume Number | 91 |
| Language | English |
| Publisher Date | 1993-02-01 |
| Access Restriction | Open |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
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