PMID- 26255968 OWN - NLM STAT- MEDLINE DCOM- 20151112 LR - 20210227 IS - 1090-2104 (Electronic) IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 465 IP - 2 DP - 2015 Sep 18 TI - High-density lipoprotein-mediated transcellular cholesterol transport in mouse aortic endothelial cells. PG - 256-61 LID - S0006-291X(15)30401-0 [pii] LID - 10.1016/j.bbrc.2015.08.011 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Miao, LiXia AU - Miao L AD - Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA; Department of Biochemistry, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. FAU - Okoro, Emmanuel U AU - Okoro EU AD - Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA. FAU - Cao, ZhiJan AU - Cao Z AD - Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA; Department of Biochemistry, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. FAU - Yang, Hong AU - Yang H AD - Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA. FAU - Motley-Johnson, Evangeline AU - Motley-Johnson E AD - Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA. FAU - Guo, Zhongmao AU - Guo Z AD - Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA. Electronic address: zguo@mmc.edu. LA - eng GR - SC1HL101431/HL/NHLBI NIH HHS/United States GR - UL1 TR000445/TR/NCATS NIH HHS/United States GR - G12 MD007586/MD/NIMHD NIH HHS/United States GR - G12MD007586/MD/NIMHD NIH HHS/United States GR - SC1 HL101431/HL/NHLBI NIH HHS/United States GR - U54MD0007593/MD/NIMHD NIH HHS/United States GR - U54 MD007593/MD/NIMHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150807 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (ABCA1 protein, mouse) RN - 0 (ABCG1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Apolipoprotein A-I) RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, HDL) RN - 0 (RNA, Small Interfering) RN - 0 (Scarb1 protein, mouse) RN - 0 (Scavenger Receptors, Class B) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - ATP Binding Cassette Transporter 1/antagonists & inhibitors/genetics/*metabolism MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/antagonists & inhibitors/genetics/*metabolism MH - Animals MH - Aorta/cytology/*drug effects/metabolism MH - Apolipoprotein A-I/metabolism/pharmacology MH - Biological Transport/drug effects MH - Cell Polarity MH - Dose-Response Relationship, Drug MH - Endothelial Cells/cytology/*drug effects/metabolism MH - Gene Expression MH - Lipoproteins/antagonists & inhibitors/genetics/*metabolism MH - Lipoproteins, HDL/metabolism/*pharmacology MH - Mice MH - Mice, Inbred C57BL MH - Phosphatidylinositol 3-Kinase/genetics/metabolism MH - Phosphorylation/drug effects MH - Primary Cell Culture MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - RNA, Small Interfering/genetics/metabolism MH - Scavenger Receptors, Class B/antagonists & inhibitors/genetics/*metabolism PMC - PMC4576456 MID - NIHMS715777 OTO - NOTNLM OT - ATP-binding cassette transporter OT - High-density lipoprotein OT - Scavenger receptor class B type I OT - Transendothelial cholesterol transport COIS- Conflict of Interest The authors have no conflicts to disclose. EDAT- 2015/08/11 06:00 MHDA- 2015/11/13 06:00 PMCR- 2016/09/18 CRDT- 2015/08/11 06:00 PHST- 2015/07/27 00:00 [received] PHST- 2015/08/03 00:00 [accepted] PHST- 2015/08/11 06:00 [entrez] PHST- 2015/08/11 06:00 [pubmed] PHST- 2015/11/13 06:00 [medline] PHST- 2016/09/18 00:00 [pmc-release] AID - S0006-291X(15)30401-0 [pii] AID - 10.1016/j.bbrc.2015.08.011 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2015 Sep 18;465(2):256-61. doi: 10.1016/j.bbrc.2015.08.011. Epub 2015 Aug 7.