Parallel decrease of tissue factor surface exposure and increase of tissue factor microparticle release by the n-3 fatty acid docosahexaenoate in endothelial cells.

Abstract

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.

• Authors: Serena Del Turco, Giuseppina Basta, Guido Lazzerini, Monica Evangelista, Giuseppe Rainaldi, Piero Tanganelli, Marina Camera, Elena Tremoli, Raffaele De Caterina
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 98 Issue 1 Pg. 210-9 (Jul 2007) ISSN: 0340-6245 [Print] Germany
• PMID: 17598015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids, Omega-3
• Lipopolysaccharides
• Membrane Proteins
• Tumor Necrosis Factor-alpha
• Docosahexaenoic Acids
• Thromboplastin

Topics

• Cells, Cultured
• Docosahexaenoic Acids (pharmacology)
• Endothelial Cells (physiology)
• Endothelium, Vascular (cytology)
• Fatty Acids, Omega-3 (pharmacology)
• Humans
• Lipopolysaccharides
• Membrane Proteins (metabolism)
• Thromboplastin (metabolism)
• Tumor Necrosis Factor-alpha
• Umbilical Veins (cytology)