Parallel decrease of tissue factor surface exposure and increase of tissue factor microparticle release by the n-3 fatty acid docosahexaenoate in endothelial cells
Serena Del Turco 1,2, Giuseppina Basta 1, Guido Lazzerini 1, Monica Evangelista 1, Giuseppe Rainaldi 1, Piero Tanganelli 2, Marina Camera 3, Elena Tremoli 3, Raffaele De Caterina1,4
1 C.N.R. Institute of Clinical Physiology, Pisa, 2 Institute of Pathology, the University of Siena, 3 Institute of Pharmacological Sciences, University of Milan, and 4Chair of Cardiology and Center of Excellence on Aging, “G. d’Annunzio” University, Chieti; Italy
Omega-3 fatty acids, N-3 fatty acids, Tissue factor, endothelial cells, microparticles, procoagulant activity
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-α. 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 decreasedTF 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.