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(Circulation Research. 2009;104:1142.)
© 2009 American Heart Association, Inc.

Molecular Medicine

High-Density Lipoprotein Transport Through Aortic Endothelial Cells Involves Scavenger Receptor BI and ATP-Binding Cassette Transporter G1

Lucia Rohrer, Pascale M. Ohnsorg, Marc Lehner, Franziska Landolt, Franz Rinninger, Arnold von Eckardstein

From the Institute of Clinical Chemistry (L.R., P.M.O., M.L., F.L., A.v.E.), Center for Integrative Human Biology and Competence Center of Systems Physiology and Metabolic Diseases, University of Zurich, University Hospital Zurich, Switzerland; and University Hospital Hamburg Eppendorf (F.R.), Germany.

Correspondence to Lucia Rohrer, Institute of Clinical Chemistry, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. E-mail lucia.rohrer{at}usz.ch

Cholesterol efflux from macrophage foam cells is a rate-limiting step in reverse cholesterol transport. In this process cholesterol acceptors like high-density lipoproteins (HDL) and apolipoprotein (apo)A-I must cross the endothelium to get access to the donor cells in the arterial intima. Previously, we have shown that apoA-I passes a monolayer of aortic endothelial cells (ECs) from the apical to the basolateral side by transcytosis, which is modulated by the ATP-binding cassette transporter (ABC)A1. Here, we analyzed the interaction of mature HDL with ECs. ECs bind HDL in a specific and saturable manner. Both cell surface biotinylation experiments and immunofluorescence microscopy of HDL recovered 30% of the cell-associated HDL intracellularly. Cultivated on inserts ECs bind, internalize, and translocate HDL from the apical to the basolateral compartment in a specific and temperature-dependent manner. The size of the translocated particle was reduced, but its protein moiety remained intact. Using RNA interference, we investigated the impact of SR-BI, ABCA1, and ABCG1 on binding, internalization, and transcytosis of HDL by ECs. HDL binding was reduced by 50% and 30% after silencing of SR-BI and ABCG1, respectively, but not at all after diminishing ABCA1 expression. Knock down of SR-BI and, even more so, ABCG1 reduced HDL transcytosis but did not affect inulin permeability. Cosilencing of both proteins did not further reduce HDL binding, internalization, or transport. In conclusion, ECs transcytose HDL by mechanisms that involve either SR-BI or ABCG1 but not ABCA1.

Key Words: cholesterol homeostasis • endothelial cells • lipoproteins • vascular endothelial function • vascular permeability