Lymphatic Vessels Are Essential for the Removal of Cholesterol from Peripheral Tissues by SR-BI-Mediated Transport of HDL

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 impair...

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Bibliographic Details
Published in:Cell metabolism 2013-05, Vol.17 (5), p.671-684
Main Authors: Lim, Hwee Ying, Thiam, Chung Hwee, Yeo, Kim Pin, Bisoendial, Radjesh, Hii, Chung Shii, McGrath, Kristine C.Y., Tan, Kar Wai, Heather, Alison, Alexander, J. Steven Jonathan, Angeli, Veronique
Format: Article
Language:English
Subjects:
Animals
Biological Transport
Cholesterol - metabolism
Endothelial Cells - metabolism
Endothelium - metabolism
Humans
Lipoproteins, HDL - metabolism
Lymphatic Vessels - metabolism
Mice
Scavenger Receptors, Class B - metabolism
Transcytosis
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Summary: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. [Display omitted] •Restoring lymphatic function in hypercholesterolemic mice improves lipid clearance•Blocking lymphatic drainage in WT mice inhibits reverse cholesterol transport•Lymphatic endothelium expresses HDL transporters•Removal of cholesterol by lymphatic requires SR-BI-mediated selective uptake of HDL
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2013.04.002