Parallel decrease of tissue factor surface exposure and increase of tissue factor microparticle release by the n-3 fatty acid docosahexaenoate in endothelial cells.
Tissue factor (TF) is expressed on the endothelium in response to inflammatory mediators, giving endothelial cells a pro-thrombotic phenotype. Since fish-derived n-3 fatty acids (FA) have been associated with reduced incidence of myocardial infarction, we investigated the endothelial effects of the most abundant n-3 FA, docosahexaenoate (DHA), on TF expression. Human umbilical vein endothelial cells were pre-incubated with DHA (or stearate and arachidonate as controls) for 48-72 hours, and then stimulated with bacterial lipopolysaccharide (LPS) or tumor necrosis factor-alpha. Pre-incubation of endothelial cells with DHA (but not stearate or arachidonate) concentration-dependently reduced surface protein exposure, independent of TF mRNA or total protein expression regulation. Conversely, DHA treatment in conjunction with activating stimuli, induced the release of endothelial TF-exposing microparticles from endothelial cells, quantitatively accounting for the decreased TF cell surface exposure. In conclusion, DHA treatment, with a time-course consistent with its incorporation in membrane phospholipids, increases the release of TF-exposing microparticles from endothelial cells, accounting for decreased endothelial cell TF surface exposure, thus potentially modifying the overall endothelial control of microparticle-related effects.
Del Turco
Serena
S
C.N.R. Institute of Clinical Physiology, Pisa, Italy.
Basta
Giuseppina
G
Lazzerini
Guido
G
Evangelista
Monica
M
Rainaldi
Giuseppe
G
Tanganelli
Piero
P
Camera
Marina
M
Tremoli
Elena
E
De Caterina
Raffaele
R
D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides; D008565:Membrane Proteins / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha; D014471:Umbilical Veins / Q000166:cytology
D015525:Fatty Acids, Omega-3; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D013925:Thromboplastin