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

• Published in: Thrombosis and haemostasis Vol. 98; no. 1; p. 210
• Main Authors: Del Turco, Serena, Basta, Giuseppina, Lazzerini, Guido, Evangelista, Monica, Rainaldi, Giuseppe, Tanganelli, Piero, Camera, Marina, Tremoli, Elena, De Caterina, Raffaele
• Format: Journal Article
• Language: English
• Published: Germany 01.07.2007
• Subjects: 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
• ISSN: 0340-6245
• DOI: 10.1160/TH06-07-0402

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.