CHOLESTEROL EFFLUX FROM HUMAN MONOCYTE-DERIVED MACROPHAGES IN THE PRESENCE OF LPA-I-A-II

Previous epidemiological studies have suggested that the LpA-I subfrac tion of HDL is more protective than the LpA-I:A-II subfraction against the development of cardiovascular disease. A possible basis for a spe cific anti-atherogenic function of LpA-I emerged from studies of chole sterol efflux from cultured mouse adipocytes. LpA-I efficiently remove d excess cholesterol from the mouse adipocytes, while LpA-I:A-II was i neffective. On the other hand, LpA-I:A-II was able to stimulate choles terol efflux from a number of other cell types including rodent macrop hages. Because of previously reported differences in HDL stimulation o f cholesterol clearance from macrophages of different origins, we dete rmined whether LpA-I:A-II could induce cholesterol efflux from culture d human monocyte-macrophages. Our findings showed that LpA-I:A-II and HDL(3) effectively stimulated cholesterol efflux from human monocyte-m acrophages enriched with cholesterol by incubation with AcLDL. LpA-I:A -II also decreased by one-half the amount of cholesterol accumulated w hen macrophages were incubated with AcLDL and LpA-I:A-II together. Thu s, it would appear that the differential anti-atherogenic effects of L pA-I:A-II and LpA-I do not derive from their effects on macrophage cho lesterol efflux. Possibly these HDL subfractions differentially affect other biologic processes that modulate the development of cardiovascu lar disease.