Very low and intermediate density lipoprotein fractions from apolipoprotein E gene-knockout mice induce cholesteryl ester accumulation in J774 macrophages

Objective To investigate the atherogenic role of very low density lipoprote in (VLDL) and intermediate density lipoprotein (IDL) fraction isolated from plasma of apolipoprotein E (apoE)-knockout mice. Methods Containing both VLDL and IDL (apoEko-VLDL/IDL), lipoprotein fractio n was isolated from plasma of apoE-knockout mice by ultracentrifugation, an d its interaction with J774 macrophages was examined together with its phys icochemical properties including lipid content, electrophoresis mobility an d apolipoprotein components. Results ApoEko-VLDL/IDL could be actively taken up by J774 macrophages, res ulting in marked cholesterol ester accumulation in the cells (55 +/- 9 nmol /mg cell protein), which was a 7-fold increase over the corresponding lever induced by low density lipoprotein and significantly higher than non-loade d group (P<0.01). Conclusion ApoEko-VLDL/IDL induced significant cholesterol ester accumulati on through an apoE independent pathway. This pathway may explain, partly th e mechanism of cholesterol deposition in arterial wall in apoE-knockout mic e.