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  • Title: Cholesterol efflux from Fu5AH cells to the serum of patients with Alagille syndrome. Importance of the hdl-phospholipids/free cholesterol ratio and of the hdl size distribution.
    Author: Davit-Spraul A, Atger V, Pourci ML, Hadchouel M, Legrand A, Moatti N.
    Journal: J Lipid Res; 1999 Feb; 40(2):328-35. PubMed ID: 9925663.
    Abstract:
    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.
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