Gewählte Publikation:
SHR
Neuro
Krebs
Kardio
Lipid
Stoffw
Microb
Robert, J; Lehner, M; Frank, S; Perisa, D; von Eckardstein, A; Rohrer, L.
Interleukin 6 stimulates endothelial binding and transport of high-density lipoprotein through induction of endothelial lipase.
Arterioscler Thromb Vasc Biol. 2013; 33(12):2699-2706
Doi: 10.1161/ATVBAHA.113.301363
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
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Frank Sasa
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- 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 I-125-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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ATP-Binding Cassette Transporters - metabolism
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Adenoviridae - genetics
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Animals -
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Biological Transport -
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Cattle -
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Cells, Cultured -
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Endothelial Cells - drug effects
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Enzyme Induction -
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Enzyme Inhibitors - pharmacology
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Genetic Vectors -
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Humans -
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Inflammation Mediators - metabolism
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Interleukin-6 - metabolism
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Lipase - antagonists & inhibitors
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Lipoproteins, HDL - metabolism
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Particle Size -
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RNA Interference -
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Scavenger Receptors, Class B - metabolism
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Transfection -
- Find related publications in this database (Keywords)
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cholesterol
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endothelial cells
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endothelial lipase
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human
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high-density lipoprotein
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interleukin-6
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inflammation