Macrophage cholesterol efflux to free apoprotein A-I in C3H and C57BL/6 mice.
Cholesterol efflux from peritoneal macrophages of mice C57BL/6 susceptible and C3H resistant to atherosclerosis was compared, using apoprotein A-I as acceptor. The elicited macrophages were labeled with 3H-cholesterol and cholesterol enriched by incubation for 24 h with acetylated LDL. After incubation for 6 or 24 h, 3H-cholesterol efflux to free apoA-I (10 microg/ml) was significantly higher with macrophages derived from C3H mice compared to C57BL/6 mice. The cells were also pretreated with 0.3-0.45 mM cyclic AMP, 10 microM 9-cis-retinoic acid or 10 microM 22(R)-hydroxycholesterol, RXR and LXR ligands. Treatment with cyclic AMP, RXR, or LXR ligands, resulted in enhancement of 3H-cholesterol efflux in both strains. Under all conditions, 3H-cholesterol efflux was significantly higher in C3H compared to C57BL/6 macrophages. In conclusion, the higher cholesterol efflux from C3H macrophages could contribute toward the resistance of this strain to diet-induced atherosclerosis despite hypercholesterolemia.
Stein
Olga
O
Department of Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ben-Naim
Mazal
M
Dabach
Yedida
Y
Hollander
Gideon
G
Stein
Yechezkiel
Y
D000077556:Alitretinoin; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D004268:DNA-Binding Proteins; D005260:Female; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D000071518:Liver X Receptors; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors; D010743:Phospholipids / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium
D016632:Apolipoprotein A-I; D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010743:Phospholipids; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014316:Tritium; C003585:22-hydroxycholesterol; D000077556:Alitretinoin; D014212:Tretinoin; D002784:Cholesterol; D000242:Cyclic AMP