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High density lipoprotein-associated lysosphingolipids reduce E-selectin expression in human endothelial cells
Jerzy-Roch Nofer1, Sven Geigenmüller, Christian Göpfert
1Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität, Münster, Germany. nofer@uni-muenster.de
Biochemical and Biophysical Research Communications
|September 27, 2003
Summary
High-density lipoproteins (HDLs) and associated lysosphingolipids inhibit E-selectin expression, a key step in atherosclerosis. This effect involves G-protein-coupled receptors and Akt kinase activation.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Atherosclerosis Research
Background:
- E-selectin mediates monocyte adhesion, an early event in atherogenesis.
- High-density lipoproteins (HDLs) inhibit cytokine-induced adhesion molecule expression, but mechanisms are unclear.
Purpose of the Study:
- Investigate lysosphingolipids (sphingosylphosphorylcholine and lysosulfatide) from HDL on TNF-alpha-induced E-selectin expression.
- Elucidate the signaling pathways involved in HDL's inhibitory effects on endothelial cells.
Main Methods:
- Utilized human umbilical endothelial cells treated with TNF-alpha.
- Assessed E-selectin expression at mRNA and protein levels.
- Employed receptor antagonists (suramin) and signaling inhibitors (pertussis toxin, LY294002, U73122).
Main Results:
- HDL, sphingosylphosphorylcholine (SPC), and lysosulfatide (LSF) significantly inhibited E-selectin expression.
- Inhibitory effects were partially reversed by suramin and pertussis toxin.
- Inhibition of Akt kinase (but not PI-PLC) abolished the restrictive effects.
Conclusions:
- HDL-associated lysosphingolipids contribute to HDL's inhibition of cytokine-induced adhesion molecule expression.
- G-protein-coupled receptor activation and protein kinase Akt signaling are implicated in this inhibitory process.