title: Lymphatic vessels are essential for the removal of cholesterol from peripheral tissues by SR-BI-mediated transport of 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.
authors.affiliation: Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.
authors.forename: Hwee Ying
authors.initials: HY
authors.lastname: Lim
authors.forename: Chung Hwee
authors.initials: CH
authors.lastname: Thiam
authors.forename: Kim Pin
authors.initials: KP
authors.lastname: Yeo
authors.forename: Radjesh
authors.initials: R
authors.lastname: Bisoendial
authors.forename: Chung Shii
authors.initials: CS
authors.lastname: Hii
authors.forename: Kristine C Y
authors.initials: KC
authors.lastname: McGrath
authors.forename: Kar Wai
authors.initials: KW
authors.lastname: Tan
authors.forename: Alison
authors.initials: A
authors.lastname: Heather
authors.forename: J Steven Jonathan
authors.initials: JS
authors.lastname: Alexander
authors.forename: Veronique
authors.initials: V
authors.lastname: Angeli
mesh_terms: D000818:Animals; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D042601:Lymphatic Vessels / Q000378:metabolism*; D051379:Mice; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D057900:Transcytosis
chemical_list: D008075:Lipoproteins, HDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol