Metabolic response of blood vessels to TNFα

  1. Abidemi Junaid
  2. Johannes Schoeman
  3. Wei Yang
  4. Wendy Stam
  5. Alireza Mashaghi
  6. Anton Jan van Zonneveld
  7. Thomas Hankemeier  Is a corresponding author
  1. Leiden University, Netherlands
  2. 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.

Data availability

The data used to generate the figures and tables can be found in the Source Data File.

Article and author information

Author details

  1. Abidemi Junaid

    Systems Pharmacology Cluster, Analytical Biosciences, LACDR, Leiden University, Leiden, Netherlands
    Competing interests
    No competing interests declared.
  2. Johannes Schoeman

    Systems Pharmacology Cluster, Analytical Biosciences, LACDR, Leiden University, Leiden, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0905-2467
  3. Wei Yang

    Systems Pharmacology Cluster, Analytical Biosciences, LACDR, Leiden University, Leiden, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3394-7570
  4. Wendy Stam

    Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    No competing interests declared.
  5. Alireza Mashaghi

    Systems Pharmacology Cluster, Medical Systems Biophysics and Bioengineering, LACDR, Leiden University, Leiden, Netherlands
    Competing interests
    No competing interests declared.
  6. Anton Jan van Zonneveld

    Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    No competing interests declared.
  7. Thomas Hankemeier

    Systems Pharmacology Cluster, Analytical Biosciences, LACDR, Leiden University, Leiden, Netherlands
    For correspondence
    hankemeier@lacdr.leidenuniv.nl
    Competing interests
    Thomas Hankemeier, TH is co-founder of MIMETAS and has some shares in MIMETAS..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7871-2073

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.

Reviewing Editor

  1. Arduino A Mangoni, Flinders Medical Centre, Australia

Publication history

  1. Received: December 27, 2019
  2. Accepted: August 2, 2020
  3. Accepted Manuscript published: August 4, 2020 (version 1)
  4. Version of Record published: September 7, 2020 (version 2)

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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  1. Abidemi Junaid
  2. Johannes Schoeman
  3. Wei Yang
  4. Wendy Stam
  5. Alireza Mashaghi
  6. Anton Jan van Zonneveld
  7. Thomas Hankemeier
(2020)
Metabolic response of blood vessels to TNFα
eLife 9:e54754.
https://doi.org/10.7554/eLife.54754

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