Human beta-migrating very low density lipoprotein induces foam cell formation in human mesangial cells

To elucidate the mechanism of foam cell formation in the mesangial region of a kidney observed in a familial type III hyperlipoproteinemic patient presenting with diabetes mellitus and nephrotic syndrome, we have examined, in the present study, the effect of human beta-VLDL (apo E2/E2) on foam cell formation in human mesangial cells, since an increase in beta-VLDL is a characteristic feature of this patient. Human beta-VLDL (apo E2/E2) induced foam cell formation in human mesangial cells. The binding of [125I]LDL to human mesangial cells was inhibited completely by both LDL and beta-VLDL. On the other hand, the binding of [125I]beta-VLDL was completely inhibited by beta-VLDL, but partially by LDL. The LDL receptor, but not the VLDL receptor was down-regulated by accumulation of cholesteryl esters. These results suggest that human beta-VLDL (apo E2/E2)-induced foam cell formation in mesangial cells is mediated through both the LDL receptor pathway and the beta-VLDL specific pathway, in which the VLDL receptor is one of the candidates.