title: High-density lipoprotein-mediated transcellular cholesterol transport in mouse aortic endothelial cells.
abstract: Accumulation of unesterified cholesterol-rich lipid vesicles in the subendothelial space contributes to atherogenesis. Transport of cholesterol from the subendothelial intima back to the circulating blood inhibits atherosclerosis development; however, the mechanism for this process has not been fully defined. Using cultured mouse aortic endothelial cells (MAECs), we observed that unesterified cholesterol can be transported across the endothelial cell monolayer from the basolateral to the apical compartment. Administration of high-density lipoprotein (HDL) or apolipoprotein AI (apoAI) to the apical compartment enhanced transendothelial cholesterol transport in a concentration-dependent manner. Knockdown of ATP-binding cassette transporter G1 (ABCG1) or scavenger receptor class B type I (SR-B1), or inhibition of SR-B1 diminished HDL-induced transendothelial cholesterol transport; while knockdown of ABCA1 reduced apoAI-mediated cholesterol transport. HDL enhanced phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt in MAECs. However, inhibition of PI3K or Akt did not reduce HDL-induced transendothelial cholesterol transport. These results suggest that HDL enhances transendothelial cholesterol transport by activation of a mechanism involving ABCA1, ABCG1 and SR-B1 but not involving PI3K and Akt.
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA; Department of Biochemistry, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: LiXia
authors.initials: L
authors.lastname: Miao
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA.
authors.forename: Emmanuel U
authors.initials: EU
authors.lastname: Okoro
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA; Department of Biochemistry, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: ZhiJan
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA.
authors.forename: Evangeline
authors.initials: E
authors.lastname: Motley-Johnson
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA. Electronic address: zguo@mmc.edu.
authors.forename: Zhongmao
authors.initials: Z
authors.lastname: Guo
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D016764:Cell Polarity; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D008074:Lipoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D051122:Scavenger Receptors, Class B; C577833:Abca1 protein, mouse; C487540:ABCG1 protein, mouse; C454739:Scarb1 protein, mouse
keywords: ATP-binding cassette transporter; High-density lipoprotein; Scavenger receptor class B type I; Transendothelial cholesterol transport