TY - JOUR TI - Metabolic response of blood vessels to TNFα AU - Junaid, Abidemi AU - Schoeman, Johannes AU - Yang, Wei AU - Stam, Wendy AU - Mashaghi, Alireza AU - van Zonneveld, Anton Jan AU - Hankemeier, Thomas A2 - Mangoni, Arduino A A2 - Barton, Matthias A2 - Dunn, Warwick VL - 9 PY - 2020 DA - 2020/08/04 SP - e54754 C1 - eLife 2020;9:e54754 DO - 10.7554/eLife.54754 UR - https://doi.org/10.7554/eLife.54754 AB - TNFα signaling in the vascular endothelium elicits multiple inflammatory responses that drive vascular destabilization and leakage. Bioactive lipids are main drivers of these processes. In vitro mechanistic studies of bioactive lipids have been largely based on two-dimensional endothelial cell cultures that, due to lack of laminar flow and the growth of the cells on non-compliant stiff substrates, often display a pro-inflammatory phenotype. This complicates the assessment of inflammatory processes. Three-dimensional microvessels-on-a-chip models provide a unique opportunity to generate endothelial microvessels in a more physiological environment. Using an optimized targeted liquid chromatography–tandem mass spectrometry measurements of a panel of pro- and anti-inflammatory bioactive lipids, we measure the profile changes upon administration of TNFα. We demonstrate that bioactive lipid profiles can be readily detected from three-dimensional microvessels-on-a-chip and display a more dynamic, less inflammatory response to TNFα, that resembles more the human situation, compared to classical two-dimensional endothelial cell cultures. KW - metabolomics KW - oxidative stress KW - inflammation KW - microvessels-on-a-chip KW - endothelial cells KW - 3D cell culture JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -