High-density lipoprotein-mediated transcellular cholesterol transport in mouse aortic endothelial cells

• Published in: Biochemical and biophysical research communications 2015-09, Vol.465 (2), p.256-261
• Main Authors: Miao, LiXia, Okoro, Emmanuel U., Cao, ZhiJan, Yang, Hong, Motley-Johnson, Evangeline, Guo, Zhongmao
• Format: Article
• Language: English
• Subjects: Animals; Aorta - cytology; Aorta - drug effects; Aorta - metabolism; Apolipoprotein A-I - metabolism; Apolipoprotein A-I - pharmacology; ATP Binding Cassette Transporter 1 - antagonists & inhibitors; ATP Binding Cassette Transporter 1 - genetics; ATP Binding Cassette Transporter 1 - metabolism; ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-binding cassette transporter; ATP-Binding Cassette Transporters - antagonists & inhibitors; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Biological Transport - drug effects; Cell Polarity; Dose-Response Relationship, Drug; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Gene Expression; High-density lipoprotein; Lipoproteins - antagonists & inhibitors; Lipoproteins - genetics; Lipoproteins - metabolism; Lipoproteins, HDL - metabolism; Lipoproteins, HDL - pharmacology; Mice; Mice, Inbred C57BL; Phosphatidylinositol 3-Kinase - genetics; Phosphatidylinositol 3-Kinase - metabolism; Phosphorylation - drug effects; Primary Cell Culture; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Scavenger receptor class B type I; Scavenger Receptors, Class B - antagonists & inhibitors; Scavenger Receptors, Class B - genetics; Scavenger Receptors, Class B - metabolism; Transendothelial cholesterol transport
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.08.011

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. •Cholesterol can be transported across the endothelial cell monolayer.•HDL and apoAI enhance transendothelial cholesterol transport.•ABCA1, ABCG1 and SR-B1 contribute to apoAI- and HDL-mediated transendothelial cholesterol transport.