Cholesterol efflux from normal and Tangier disease fibroblasts into normal, high-density lipoprotein-deficient, and apolipoprotein E-deficient plasmas.
Tangier disease (TD) fibroblasts have defective cholesterol release in the presence of lipid-free apolipoproteins. We compared normolipidemic probands and patients with apolipoprotein A-I (apoA-I) deficiency, apoE deficiency, or TD in terms of the plasma capacity to induce the efflux of [3H]-cholesterol from normal and TD fibroblasts and to esterify this cell-derived cholesterol. Compared with normal fibroblasts, TD fibroblasts released a significantly smaller fraction of [3H]-cholesterol into normal, high-density lipoprotein (HDL)-deficient, and apoE-deficient plasmas. Supplementation of apoE-deficient plasma with exogenous apoE normalized the cholesterol efflux from normal cells but did not fully restore the reduced cholesterol efflux from TD fibroblasts. Compared with control plasma, HDL- and apoE-deficient plasmas had a significantly reduced activity to esterify cell-derived cholesterol. Cholesterol derived from TD fibroblasts was less available for esterification in either patient or normal plasmas than cholesterol derived from normal cells. The esterification defect of TD cell-derived cholesterol was more pronounced in patient plasmas than in control plasma. We conclude that (1) apoA-I and, to a lesser degree, apoE are important determinants of the cholesterol efflux and esterification capacity of plasma, (2) TD fibroblasts have a reduced capacity to release cholesterol into the plasma, and (3) TD cell-derived cholesterol is less available for esterification in plasma than cholesterol from normal fibroblasts. The absence of distinct apoA-I- or apoE-containing subclasses aggravates the defective efflux and esterification of cholesterol derived from TD cells.
Schuler-Lüttmann
S
S
Institut für Arterioskleroseforschung an der Universität Münster, Germany.
Zhu
Y
Y
Hoffmann
M
M
März
W
W
Feussner
G
G
Wieland
H
H
Assmann
G
G
von Eckardstein
A
A
D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency*; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood* / Q000737:chemistry; D003470:Culture Media; D015180:Electrophoresis, Gel, Two-Dimensional; D004951:Esterification; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood / Q000172:deficiency*; D008297:Male; D008875:Middle Aged; D013631:Tangier Disease / Q000097:blood*
D001057:Apolipoproteins E; D003470:Culture Media; D008055:Lipids; D008075:Lipoproteins, HDL; D002784:Cholesterol