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Apolipoprotein A-I stabilizes phospholipid lamellae and thus prolongs nucleation time in model bile systems: an
1First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Abstract:
To explore the mechanisms whereby apolipoprotein A-I inhibits the nucleation of cholesterol crystals, we performed an ultrastructural study using supersaturated model bile systems. Vesicles, micelles and phospholipid lamellae were consistently separated by gel permeation chromatography either in the absence or presence of apolipoprotein A-I. Furthermore, apolipoprotein A-I coeluted with phospholipid lamellae. A sequential study using transmission electron microscopy revealed that phospholipid lamellae without apolipoprotein A-I showed a rapid transformation, with formation of multilamellae and fusion followed by microcrystal nucleation. In contrast, lamellae with apolipoprotein A-I showed little transformation. In conclusion, apolipoprotein A-I stabilizes the phospholipid lamellae, thereby inhibiting the nucleation of cholesterol crystals in supersaturated model bile systems.