Lymphatic vessels are essential for the removal of cholesterol from peripheral tissues by SR-BI-Mediated transport of HDL

Lim, HY; Thiam, CH; Yeo, KP; Bisoendial, R; Hii, CS; McGrath, KCY; Tan, KW; Heather, A; Alexander, JSJ; Angeli, V

Lymphatic vessels are essential for the removal of cholesterol from peripheral tissues by SR-BI-Mediated transport of HDL

Lim, HY Thiam, CH Yeo, KP Bisoendial, R Hii, CS McGrath, KCY

Tan, KW Heather, A Alexander, JSJ Angeli, V

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Publication Type:: Journal Article
Citation:: Cell Metabolism, 2013, 17 (5), pp. 671 - 684
Issue Date:: 2013-05-07

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Field	Value	Language
dc.contributor.author	Lim, HY	en_US
dc.contributor.author	Thiam, CH	en_US
dc.contributor.author	Yeo, KP	en_US
dc.contributor.author	Bisoendial, R	en_US
dc.contributor.author	Hii, CS	en_US
dc.contributor.author	McGrath, KCY https://orcid.org/0000-0002-6244-3929	en_US
dc.contributor.author	Tan, KW	en_US
dc.contributor.author	Heather, A	en_US
dc.contributor.author	Alexander, JSJ	en_US
dc.contributor.author	Angeli, V	en_US
dc.date.available	2013-04-01	en_US
dc.date.issued	2013-05-07	en_US
dc.identifier.citation	Cell Metabolism, 2013, 17 (5), pp. 671 - 684	en_US
dc.identifier.issn	1550-4131	en_US
dc.identifier.uri	http://hdl.handle.net/10453/26538
dc.description.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.	en_US
dc.relation.ispartof	Cell Metabolism	en_US
dc.relation.isbasedon	10.1016/j.cmet.2013.04.002	en_US
dc.subject.classification	Endocrinology & Metabolism	en_US
dc.subject.mesh	Endothelium	en_US
dc.subject.mesh	Endothelial Cells	en_US
dc.subject.mesh	Lymphatic Vessels	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Cholesterol	en_US
dc.subject.mesh	Lipoproteins, HDL	en_US
dc.subject.mesh	Biological Transport	en_US
dc.subject.mesh	Scavenger Receptors, Class B	en_US
dc.subject.mesh	Transcytosis	en_US
dc.title	Lymphatic vessels are essential for the removal of cholesterol from peripheral tissues by SR-BI-Mediated transport of HDL	en_US
dc.type	Journal Article
utslib.citation.volume	5	en_US
utslib.citation.volume	17	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Arts and Social Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Medical and Molecular Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	5	en_US
pubs.publication-status	Published	en_US
pubs.volume	17	en_US

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/26538