Human ApoA-IV overexpression in transgenic mice induces cAMP-stimulated cholesterol efflux from J774 macrophages to whole serum

The role of apolipoprotein A-IV (apoA-IV) in lipoprotein metabolism has not been established. The aim of the present study was to investigate the role of apoA-IV in reverse cholesterol transport by comparing cellular choleste rol efflux to serum or serum fractions from control mice and from mice tran sgenic for human apoA-IV (HuA-IVTg mice). When Fu5AH hepatoma cells were us ed, the cholesterol efflux to serum from either control or transgenic mice was similar. When control J774 macrophage cells were used, a comparison of efflux to serum or lipoprotein-deficient serum (LPDS) failed to demonstrate any differences between control and transgenic mice. In contrast, when the J774 cells were pretreated with cAMP, there was a stimulation of efflux to whole serum or LPDS from HuA-IVTg mice. cAMP treatment had no effect on ef flux to serum or LPDS from control mice. Pretreatment of the cells with cAM P did not enhance the efflux response to high density lipoprotein isolated from HuA-IVTg mouse serum. Our results suggest that apoA-IV, unassociated w ith high density lipoprotein particles, is responsible for enhanced cholest erol efflux. This study illustrates the role of lipid-free apolipoproteins in mediating cellular cholesterol efflux with use of a biological fluid and is potentially of physiological relevance, especially in apolipoprotein-ri ch extravascular fluids.