Cholesterol efflux from human monocyte-derived macrophages in the presence of LpA-I:A-II.
Previous epidemiological studies have suggested that the LpA-I subfraction of HDL is more protective than the LpA-I:A-II subfraction against the development of cardiovascular disease. A possible basis for a specific anti-atherogenic function of LpA-I emerged from studies of cholesterol efflux from cultured mouse adipocytes. LpA-I efficiently removed excess cholesterol from the mouse adipocytes, while LpA-I:A-II was ineffective. On the other hand, LpA-I:A-II was able to stimulate cholesterol efflux from a number of other cell types including rodent macrophages. Because of previously reported differences in HDL stimulation of cholesterol clearance from macrophages of different origins, we determined whether LpA-I:A-II could induce cholesterol efflux from cultured human monocyte-macrophages. Our findings showed that LpA-I:A-II and HDL3 effectively stimulated cholesterol efflux from human monocyte-macrophages enriched with cholesterol by incubation with AcLDL. LpA-I:A-II also decreased by one-half the amount of cholesterol accumulated when macrophages were incubated with AcLDL and LpA-I:A-II together. Thus, it would appear that the differential anti-atherogenic effects of LpA-I:A-II and LpA-I do not derive from their effects on macrophage cholesterol efflux. Possibly these HDL subfractions differentially affect other biologic processes that modulate the development of cardiovascular disease.
Skarlatos
S I
SI
Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Duverger
N
N
Rader
D
D
Kruth
H S
HS
D002318:Cardiovascular Diseases / Q000517:prevention & control; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects; D010316:Particle Size
D017270:Lipoprotein(a); D008075:Lipoproteins, HDL; C078260:lipoprotein A-I; D002784:Cholesterol