Metabolic response of blood vessels to TNFα
- Leiden University, Netherlands
- Leiden University Medical Center, Netherlands
Abstract
TNFa 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 TNFa. 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 TNFa, that resembles more the human situation, compared to classical two-dimensional endothelial cell cultures.
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Author details
Funding
Hartstichting (RECONNECT CVON Groot)
- Abidemi Junaid
- Anton Jan van Zonneveld
- Thomas Hankemeier
ZonMw (114022501)
- Abidemi Junaid
- Anton Jan van Zonneveld
- Thomas Hankemeier
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (16249)
- Alireza Mashaghi
- Thomas Hankemeier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Junaid et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Metabolic response of blood vessels to TNFα
eLife 9:e54754.
https://doi.org/10.7554/eLife.54754
