1. Lymphatic Vessels Are Essential for the Removal of Cholesterol from Peripheral Tissues by SR-BI-Mediated Transport of HDL
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Hwee Ying Lim, Chung Hwee Thiam, Kim Pin Yeo, Alison K. Heather, Kristine C.Y. McGrath, Chung Shii Hii, J. Steven Alexander, Radjesh J. Bisoendial, Kar Wai Tan, and Veronique Angeli
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Genetically modified mouse ,Physiology ,government.form_of_government ,Biology ,Pharmacology ,chemistry.chemical_compound ,Endocrinology & Metabolism ,Mice ,Animals ,Humans ,Endothelium ,Scavenger receptor ,Molecular Biology ,Lymphatic Vessels ,Cholesterol ,Reverse cholesterol transport ,Endothelial Cells ,Biological Transport ,Cell Biology ,Scavenger Receptors, Class B ,Lymphatic Endothelium ,Lymphatic system ,chemistry ,Transcytosis ,Mediated transport ,Immunology ,government ,lipids (amino acids, peptides, and proteins) ,Lipoproteins, HDL - Abstract
Removal of cholesterol from peripheral tissues to the bloodstream via reverse cholesterol transport (RCT) is a process of major biological importance. Here we demonstrate that lymphatic drainage is required for RCT. We have previously shown that hypercholesterolemia in mice is associated with impaired lymphatic drainage and increased lipid accumulation in peripheral tissues. We now show that restoration of lymphatic drainage in these mice significantly improves cholesterol clearance. Conversely, obstruction of lymphatic vessels in wild-type mice significantly impairs RCT. Finally, we demonstrate using silencing RNA interference, neutralizing antibody, and transgenic mice that removal of cholesterol by lymphatic vessels is dependent on the uptake and transcytosis of HDL by scavenger receptor class B type I expressed on lymphatic endothelium. Collectively, this study challenges the current view that lymphatic endothelium is a passive exchange barrier for cholesterol transport and provides further evidence for its interplay with lipid biology in health and disease. © 2013 Elsevier Inc.
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