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Interleukin 6 stimulates endothelial binding and transport of high-density lipoprotein through induction of endothelial lipase


Robert, Jérôme; Lehner, Marc; Frank, Sasa; Perisa, Damir; von Eckardstein, Arnold; Rohrer, Lucia (2013). Interleukin 6 stimulates endothelial binding and transport of high-density lipoprotein through induction of endothelial lipase. Arteriosclerosis, Thrombosis, and Vascular Biology, 33(12):2699-2706.

Abstract

OBJECTIVE: In the reverse cholesterol transport pathway, high-density lipoprotein (HDL) passes the endothelial cell barrier by mechanisms involving the scavenger receptor class B type I and the ATP-binding cassette G1. However, little is known on how inflammation influences this transendothelial transport.
APPROACH AND RESULTS: On stimulation with interleukin-6, cultivated primary endothelial cells showed increased binding and transport of (125)I-HDL without changing the expression of scavenger receptor class B type I and ATP-binding cassette G1. Therefore, we analyzed the involvement of endothelial lipase (EL), a known HDL-binding protein expressed by endothelial cells. Here, we show an increased EL expression after interleukin-6 stimulation. Moreover, using pharmacological inhibitors or RNA interference against EL, we demonstrated its participation in HDL binding and transport through the endothelium. Furthermore, adenovirus-mediated transfection of endothelial cells with either catalytically active or nonactive EL revealed that EL facilitates the endothelial binding and transport by both bridging and lipolysis of HDL. EL was also found responsible for the reduction of HDL particle size occurring during the specific transport through a monolayer of endothelial cells. Finally, pharmacological inhibition of EL reversed the inducing effect of interleukin-6 on HDL binding and transport.
CONCLUSIONS: Interleukin-6 stimulates the translocation of HDL through the endothelium, the first step in reverse cholesterol transport pathway, by enhancing EL expression. In addition, we demonstrated the role of EL in the transendothelial transport of HDL.

Abstract

OBJECTIVE: In the reverse cholesterol transport pathway, high-density lipoprotein (HDL) passes the endothelial cell barrier by mechanisms involving the scavenger receptor class B type I and the ATP-binding cassette G1. However, little is known on how inflammation influences this transendothelial transport.
APPROACH AND RESULTS: On stimulation with interleukin-6, cultivated primary endothelial cells showed increased binding and transport of (125)I-HDL without changing the expression of scavenger receptor class B type I and ATP-binding cassette G1. Therefore, we analyzed the involvement of endothelial lipase (EL), a known HDL-binding protein expressed by endothelial cells. Here, we show an increased EL expression after interleukin-6 stimulation. Moreover, using pharmacological inhibitors or RNA interference against EL, we demonstrated its participation in HDL binding and transport through the endothelium. Furthermore, adenovirus-mediated transfection of endothelial cells with either catalytically active or nonactive EL revealed that EL facilitates the endothelial binding and transport by both bridging and lipolysis of HDL. EL was also found responsible for the reduction of HDL particle size occurring during the specific transport through a monolayer of endothelial cells. Finally, pharmacological inhibition of EL reversed the inducing effect of interleukin-6 on HDL binding and transport.
CONCLUSIONS: Interleukin-6 stimulates the translocation of HDL through the endothelium, the first step in reverse cholesterol transport pathway, by enhancing EL expression. In addition, we demonstrated the role of EL in the transendothelial transport of HDL.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
540 Chemistry
Language:English
Date:2013
Deposited On:22 Oct 2013 06:58
Last Modified:07 Dec 2017 23:01
Publisher:Lippincott, Williams & Wilkins
ISSN:1079-5642
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1161/ATVBAHA.113.301363
PubMed ID:24115033

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