Omega-3 fatty acids modulate Weibel-Palade body degranulation and actin cytoskeleton rearrangement in PMA-stimulated human umbilical vein endothelial cells
Introduction. Von Willebrand factor (vWF), released from endothelial storage granules (Weibel-Palade bodies; WPBs), is thrombogenic (Ruggeri, 2007). Although anti-thrombotic effects have been ascribed to long chain omega- 3 polyunsaturated fatty acids (LC n-3 PUFAs), their mechanisms of action have not been fully investigated. Aims. To determine whether LC n-3 PUFAs regulate WPB degranulation in stimulated human cultured umbilical vein endothelial cells (HUVECs). Methods. HUVECs were incubated with or without 75 or 120 μM docosahexaenoic acid or eicosapentaenoic acid for 5 days at 37°C. WPB degranulation was stimulated using phorbol 12-myristate 13-acetate (PMA), and this was assessed by immunocytochemical staining for vWF. Actin reorganisation was determined using phalloidin-TRITC staining. Results. We found that PMA stimulated WPB degranulation, and that this was reduced by prior incubation of cells with 120 μM LC n-3 PUFAs (control: 75.7±6.7%, PMA: 5.7±1.5%, PMA+DHA: 20.7±1.3%, PMA+EPA: 17±5.9% of granulated HUVECs, one-way ANOVA, n=3, p less than 0.05). In these cells, WPBs had rounded rather than rod-shaped morphology and localised to the perinuclear region, suggesting interference with cytoskeletal remodelling that is necessary for complete WPB degranulation. In line with this, actin rearrangement was altered in cells containing perinuclear WPBs, where cells exhibited a thickened actin rim in the absence of prominent cytoplasmic stress fibres. Discussion. These findings indicate that LC n-3 PUFAs provide some protection against WBP degranulation, and may contribute to an improved understanding of the anti-thrombotic effects previously attributed to LC n-3 PUFAs.
Relation
2013 Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) Annual Scientific Meeting: Breaking down the silos - academia, industry and the government collaboratively developing medicines, Melbourne, Australia 1-4 December 2013
Relation
2013 Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) Annual Scientific Meeting Book of Abstracts / pp.84
Research Publications
Omega-3 fatty acids modulate Weibel-Palade body degranulation and actin cytoskeleton rearrangement in PMA-stimulated human umbilical vein endothelial cells
185 Visitors
0 Downloads
Disclaimer |
Privacy |
