We have previously described the
lipoprotein abnormalities in cholestatic children with
paucity of interlobular bile ducts (PILBD), and we have shown that two different profiles emerged among these patients, depending on the level of
lecithin:cholesterol acyltransferase (LCAT) activity. Reduced LCAT activity was associated with
hypo-alpha-lipoproteinemia (group I) whereas normal LCAT activity was associated with hyper-alpha-lipoproteinemia (group II). In both groups,
high density lipoproteins (HDL) were enriched with
phospholipids and LpA-I particles were predominant. Here, we have investigated the ability of serum and of isolated HDL, obtained from PILBD and control subjects, to promote cellular
cholesterol efflux, from Fu5AH rat
hepatoma cells. The mean fractional efflux to 5% serum in each group was, on average, following the differences in HDL concentrations (control: 30.1 +/- 4.2%; group I: 23.7 +/- 7.9%, ns; group II: 44.2 +/- 6.5%, P < 0.001). The variations in efflux values in group II were positively correlated to the variations in HDL-PL concentrations (P < 0.0001) and in HDL-PL to serum
apo-AI ratio (P < 0.003). By contrast, the variation in efflux in group I was only positively related to the large range of HDL-PL to free
cholesterol (FC) ratio values (P < 0.0004). Fractional efflux to isolated HDL, measured at a constant HDL-PL amount, confirmed this relationship (P < 0.0001). Two-dimensional gel electrophoresis of the HDL size and
apo A-I distribution in serum, revealed that small size HDL(3) and
pre-beta HDL were predominant in the serum of patients from group I, especially those exhibiting low HDL-PL to FC ratio, whereas in the serum of patients from group II, both small HDL(3) and large HDL2 were present. These results suggest that a combination of an imbalance between
phospholipids and free
cholesterol in the HDL particles and a deficit in large acceptors of
cholesterol will be responsible for an impairment of cellular
cholesterol efflux in PILBD patients with reduced
lecithin:cholesterol acyltransferase activity.-Davit-Spraul, A., V. Atger, M. L. Pourci, M. Hadchouel, A. Legrand, and N. Moatti.
Cholesterol efflux from Fu5AH cells in the serum of patients with
Alagille syndrome: importance of the HDL-
phospholipids/free
cholesterol ratio and of the HDL size distribution.