title: Imbalanced response of ATP-binding cassette transporter A1 and CD36 expression to increased oxidized low-density lipoprotein loading contributes to the development of THP-1 derived foam cells.
abstract: ATP-binding cassette transporter A1 (ABCA1) and CD36, type B scavenger receptor, function as the key mediators of macrophages cholesterol efflux and intake, respectively. However, their contribution to development of foam cells still remains uncertain. We here examined the effects of increased oxidized low-density lipoprotein (oxLDL) loading on the ABCA1 and CD36 expression, and lipid accumulation in THP-1 macrophages. The cultured THP-1 macrophages were treated with different copper-oxLDL concentrations. The intracellular lipid contents and cholesterol efflux were measured, and the ABCA1 and CD36 expression were assessed. We found that expression of ABCA1 and CD36 were coordinately induced upon low to moderate doses of oxLDL loading. However, higher doses of oxLDL stimulation resulted in the imbalanced expression of ABCA1 and CD36 proteins with more preferentially suppressed ABCA1 protein, attenuated cholesterol efflux and development of THP-1 derived foam cells. The PPAR-γ expression was remarkably induced, and PPAR-γ agonist, pioglitazone, significantly promoted the ABCA1 and CD36 expression. Additionally, ABCA1 and CD36 proteins were strong colocalized in THP-1 macrophages membrane. In conclusion, the more preferentially suppressed ABCA1 expression as compared with CD36 at higher doses of oxLDL stimulation may be the initiator for the formation of macrophage-derived foam cells.
authors.affiliation: Department of Neurology; Cardiology Center, Ningbo First Hospital, Ningbo University, Ningbo 315010, People's Republic of China; Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an Jiaotong University, Xi'an 710068, People's Republic of China; Key Laboratory of Molecular Biology, Ningbo First Hospital, Ningbo University, Ningbo 315010, People's Republic of China; Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an 710061, People's Republic of China; and Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an 710061, People's Republic of China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Liu
authors.forename: Han-Bin
authors.initials: HB
authors.lastname: Cui
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Chen
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Chen
authors.forename: Sheng-Huang
authors.initials: SH
authors.lastname: Wang
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Du
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Zhou
authors.forename: Ruo-Chi
authors.initials: RC
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Chang-Cong
authors.initials: CC
authors.lastname: Cui
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D001483:Base Sequence; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018955:CD36 Antigens; D017931:DNA Primers; D008077:Lipoproteins, LDL; D047495:PPAR gamma; C099252:oxidized low density lipoprotein
keywords: ABCA1; CD36; macrophage cholesterol homeostasis; oxidized LDL; peroxisome proliferator-activated receptors