title: ABCA1 (ATP-Binding Cassette Transporter A1) Mediates ApoA-I (Apolipoprotein A-I) and ApoA-I Mimetic Peptide Mobilization of Extracellular Cholesterol Microdomains Deposited by Macrophages.
abstract: OBJECTIVE
  We examined the function of ABCA1 (ATP-binding cassette transporter A1) in ApoA-I (apolipoprotein A-I) mobilization of cholesterol microdomains deposited into the extracellular matrix by cholesterol-enriched macrophages. We have also determined whether an ApoA-I mimetic peptide without and with complexing to sphingomyelin can mobilize macrophage-deposited cholesterol microdomains.
  
  
  RESULTS
  Extracellular cholesterol microdomains deposited by cholesterol-enriched macrophages were detected with a monoclonal antibody, 58B1. ApoA-I and an ApoA-I mimetic peptide 5A mobilized cholesterol microdomains deposited by ABCA1+/+macrophages but not by ABCA1-/-macrophages. In contrast, ApoA-I mimetic peptide 5A complexed with sphingomyelin could mobilize cholesterol microdomains deposited by ABCA1-/-macrophages.
  
  
  CONCLUSIONS
  Our findings show that a unique pool of extracellular cholesterol microdomains deposited by macrophages can be mobilized by both ApoA-I and an ApoA-I mimetic peptide but that mobilization depends on macrophage ABCA1. It is known that ABCA1 complexes ApoA-I and ApoA-I mimetic peptide with phospholipid, a cholesterol-solubilizing agent, explaining the requirement for ABCA1 in extracellular cholesterol microdomain mobilization. Importantly, ApoA-I mimetic peptide already complexed with phospholipid can mobilize macrophage-deposited extracellular cholesterol microdomains even in the absence of ABCA1.
authors.affiliation: From the Experimental Atherosclerosis Section (X.J., Y.L., H.S.K.) and Lipoprotein Metabolism Section (D.S., B.V., A.T.R.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel (L.A.).
authors.forename: Xueting
authors.initials: X
authors.lastname: Jin
authors.affiliation: From the Experimental Atherosclerosis Section (X.J., Y.L., H.S.K.) and Lipoprotein Metabolism Section (D.S., B.V., A.T.R.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel (L.A.).
authors.forename: Denis
authors.initials: D
authors.lastname: Sviridov
authors.affiliation: From the Experimental Atherosclerosis Section (X.J., Y.L., H.S.K.) and Lipoprotein Metabolism Section (D.S., B.V., A.T.R.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel (L.A.).
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From the Experimental Atherosclerosis Section (X.J., Y.L., H.S.K.) and Lipoprotein Metabolism Section (D.S., B.V., A.T.R.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel (L.A.).
authors.forename: Boris
authors.initials: B
authors.lastname: Vaisman
authors.affiliation: From the Experimental Atherosclerosis Section (X.J., Y.L., H.S.K.) and Lipoprotein Metabolism Section (D.S., B.V., A.T.R.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel (L.A.).
authors.forename: Lia
authors.initials: L
authors.lastname: Addadi
authors.affiliation: From the Experimental Atherosclerosis Section (X.J., Y.L., H.S.K.) and Lipoprotein Metabolism Section (D.S., B.V., A.T.R.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel (L.A.).
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.affiliation: From the Experimental Atherosclerosis Section (X.J., Y.L., H.S.K.) and Lipoprotein Metabolism Section (D.S., B.V., A.T.R.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel (L.A.). kruthh@nhlbi.nih.gov.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Kruth
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D018716:Molecular Mimicry; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D010641:Phenotype; D013109:Sphingomyelins / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D002784:Cholesterol; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D013109:Sphingomyelins; C000613704:5A peptide; C577836:ABCA1 protein, human; C577833:Abca1 protein, mouse; C505693:APOA1 protein, human
keywords: apolipoprotein A-I; atherosclerosis; cholesterol; extracellular matrix; macrophages