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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1746-1754.)
© 1995 American Heart Association, Inc.

Articles

Generation of Pre-ß₁-HDL and Conversion Into -HDL

Evidence for Disturbed HDL Conversion in Tangier Disease

Yadong Huang; Arnold von Eckardstein; Shili Wu; Claus Langer; Gerd Assmann

From the Institut für Arterioskleroseforschung an der Universität Münster (Y.H., S.W., G.A.) and the Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium, Westfälische Wilhelms-Universität Münster (A. von E., C.L., G.A.), Federal Republic of Germany.

Correspondence to Arnold von Eckardstein, Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Str 33, D-48129 Münster, Federal Republic of Germany.

Abstract HDL encompasses several apoA-I–containing particles that differ by size and show pre-ß- or -mobility on agarose gel electrophoresis: pre-ß₁-LpA-I, pre-ß₂-LpA-I, pre-ß₃-LpA-I, -LpA-I₂, and -LpA-I₃. The quantitatively minor subclass pre-ß₁-LpA-I serves as an initial acceptor of cell-derived cholesterol. In this study, we generated a pre-ß₁-LpA-I–like particle in vitro by the incubation of biotinylated apoA-I with cholesterol-loaded macrophages. Both native pre-ß₁-LpA-I and in vitro–generated pre-ß₁-LpA-I were indistinguishable from lipid-free apoA-I by two-dimensional nondenaturing polyacrylamide gradient gel electrophoresis but exhibited a different size upon gel filtration. In vitro–generated biotin–pre-ß₁-LpA-I took up twofold to threefold more [³H]cholesterol from labeled fibroblasts during a 1-minute pulse incubation than lipid-free apoA-I. The in vitro conversion of biotin–pre-ß₁-LpA-I was investigated in the presence of plasmas of healthy probands and patients with Tangier disease, with apoA-I deficiency, and with lecithin-cholesterol acyltransferase (LCAT) deficiency. Incubation of biotin–pre-ß₁-LpA-I with plasmas either from normoalphalipoproteinemic probands or from a patient with apoA-I deficiency generated a biotinylated particle with the size and electrophoretic mobility of -LpA-I₂. This conversion was sensitive to heating at 56°C but not to the removal of calcium. Inhibition of LCAT by dithiobisnitrobenzoic acid led to the formation of -LpA-I₃ instead of -LpA-I₂. Incubation of biotin–pre-ß₁-LpA-I with the plasma of an LCAT-deficient patient also led to the generation of biotin–-LpA-I₃ instead of -LpA-I_2. By contrast, incubation of biotin–pre-ß₁-LpA-I with plasma of patients with Tangier disease did not cause the disappearance of biotin–pre-ß₁-LpA-I and the formation of biotin–-LpA-I. However, co-incubation of Tangier disease plasma or of pre-ß₁-LpA-I isolated from Tangier disease plasma with apoA-I–deficient plasma generated -LpA-I₂. In conclusion, our data indicate that (1) pre-ß₁-LpA-I can be formed in vitro by the interaction of free apoA-I with cholesterol-loaded macrophages, (2) both normal and apoA-I–deficient plasmas contain a factor that converts pre-ß₁-LpA-I into -LpA-I, and (3) this factor is absent in the plasma of patients with Tangier disease.

Key Words: HDL subclasses • reverse cholesterol transport • apoA-I deficiency • familial LCAT deficiency • cholesterol efflux

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