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SHR Neuro Krebs Kardio Lipid

Riederer, M; Lechleitner, M; Hrzenjak, A; Koefeler, H; Desoye, G; Heinemann, A; Frank, S.
Endothelial lipase (EL) and EL-generated lysophosphatidylcholines promote IL-8 expression in endothelial cells.
Atherosclerosis. 2011; 214(2):338-344 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Desoye Gernot
Frank Saša
Heinemann Akos
Hrzenjak Andelko
Köfeler Harald
Riederer Monika
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Number of Figures: 4
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Abstract:
Objective: Previously we identified palmitoyl-lysophosphatidylcholine (LPC 16:0), as well as linoleoyl-, arachidonoyl-and oleoyl-LPC (LPC 18:2, 20:4 and 18:1) as the most prominent LPC species generated by the action of endothelial lipase (EL) on high-density lipoprotein (HDL). In the present study, the impact of EL and EL-generated LPC on interleukin-8 (IL-8) synthesis was examined in vitro in primary human aortic endothelial cells (HAEC) and in mice. Methods and Results: Adenovirus-mediated overexpression of the catalytically active EL, but not its inactive mutant, increased endothelial synthesis of IL-8 mRNA and protein in a time- and HDL-concentration-dependent manner. While LPC 18:2 was inactive, LPC 16:0, 18:1 and 20:4 promoted IL-8 mRNA-and protein-synthesis, differing in potencies and kinetics. The effects of all tested LPC on IL-8 synthesis were completely abrogated by addition of BSA and chelation of intracellular Ca2+. Underlying signaling pathways also included NFkB, p38-MAPK, ERK, PKC and PKA. In mice, adenovirus-mediated overexpression of EL caused an elevation in the plasma levels of MIP-2 (murine IL-8 analogue) accompanied by a markedly increased plasma LPC/PC ratio. Intravenously injected LPC also raised MIP-2 plasma concentration, however to a lesser extent than EL overexpression. Conclusion: Our results indicate that EL and EL-generated LPC, except of LPC 18:2, promote endothelial IL-8 synthesis, with different efficacy and kinetics, related to acyl-chain length and degree of saturation. Accordingly, due to its capacity to modulate the availability of the pro-inflammatory and pro-adhesive chemokine IL-8, EL should be considered an important player in the development of atherosclerosis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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Animals -
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Cells, Cultured -
Chemokine CXCL2 - blood
Cyclic AMP-Dependent Protein Kinases - metabolism
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Injections, Intravenous -
Interleukin-8 - biosynthesis Interleukin-8 - genetics
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Lipase - genetics Lipase - metabolism
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Mice -
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Find related publications in this database (Keywords)
Endothelial lipase (EL)
Lysophosphatidylcholine (LPC)
IL-8
Endothelial cells
Atherosclerosis
Adenovirus
Acyl-chain
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